As a child, Rue Bennett struggles with mental disorders and her father's death from cancer, which leads to a drug addiction. Now 16, Rue returns home from rehab and immediately goes to her dealer Fez O'Neill for drugs. Jules Vaughn, a new trans girl in town, is invited by her friend, Kat Hernandez, to a party hosted by popular college freshman Chris McKay. Before the party, Jules hooks up at a motel with an older man from a hookup app after lying about her age. At the party, Kat loses her virginity. McKay's high school girlfriend Cassie Howard gets upset when he chokes her during sex, but he stops and they discuss it. Maddy Perez, who recently broke up with star quarterback Nate Jacobs, has public revenge sex with Tyler, whom she just met at the party. Angered by this, Nate drunkenly harasses Jules, and she threatens him with a knife before cutting her arm. Rue introduces herself to Jules and goes home with her. Nate returns home and encounters his father, Cal, who was Jules's hookup.

An 11-year-old Nate discovers his father's porn collection of homemade videos featuring him having sex with young gay men and transgender women. Nate becomes a successful quarterback who struggles with anger issues and sexual insecurities. In the present, Nate breaks into Tyler's house and severely beats him, accusing him of raping underage Maddy at McKay's party after Maddy falsely told him she blacked out. On the first day of school, Rue breaks down in front of the class after being asked to talk about her summer. Afterwards, Cassie's sister Lexi attempts to comfort Rue, but she lashes out. Rue reminisces about trying oxycodone for the first time at 13, stealing from her dying father's prescription. Kat discovers that the amateur video of her having sex at McKay's party is popular online and realizes she can make money as a camgirl. McKay spends time with Cassie and accuses her of being too sexual. Mouse, Fez's intimidating supplier, coerces Rue into trying fentanyl. Jules starts messaging on the dating app with Nate, who catfishes her by adopting the name "Tyler" and the username "shyguy118".

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The title of this episode is a reference to the 2006 Birdman and Lil Wayne song "Stuntin' Like My Daddy".^[6]

A young Kat abruptly gains weight on a family vacation. Her middle-school boyfriend, Daniel, breaks up with her. She retreats into the world of romance and becomes a popular online fan fiction writer. In the present, Kat starts to work as a camgirl, catering to a series of submissive men with financial domination fetishes. Jules tells Rue she will stop being friends with her if she keeps using drugs. At her Narcotics Anonymous meeting, Rue says she is 60 days sober; another attendee, Ali Muhammed, tells her he knows she is lying. Rue helps Jules take nude photos of herself after Nate sends her a "dick pic", and she steals pills from Jules's kitchen. Maddy is shocked to find pictures of penises on Nate's phone. Rue and Jules argue after Jules reveals her plans to meet "Tyler" alone at night. Shortly thereafter, Rue goes to Jules's house to apologize and ends up kissing her. Panicked at the thought of alienating Jules, Rue visits Fez to get drugs; Fez, afraid for her well-being, refuses to sell her any and locks her out of his house. Upset, Rue tearfully blames Fez for her addiction. She then calls Ali for help.

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The title of this episode is a reference to the 2002 Nas song "Made You Look".

An 11-year-old Jules is admitted to a psychiatric hospital by her mother because of her depression and problems with self-harming. Her parents later separate and she begins transitioning to deal with her gender dysphoria. In the present, Nate and Maddy have an argument at the carnival, and Nate grabs her by the throat after she publicly insults his family. McKay upsets Cassie by refusing to acknowledge her as his girlfriend. Cassie and Maddy take MDMA, and Cassie flirts with Daniel. Kat hangs out with Ethan, a classmate who has a crush on her, but becomes jealous when she incorrectly assumes he is flirting with another girl and ends up having sex with an older boy. Rue looks for her sister, Gia, and finds her high on marijuana. Jules recognizes Cal as her hookup. Cal confronts Jules, begging her not to reveal their secret; she assures him that she will not tell anyone. After the carnival, Jules meets up with "Tyler" and discovers he is Nate. Nate blackmails her, threatening to report the nude pictures Jules has sent him as child pornography unless she keeps quiet about her relationship with his father. Jules goes to Rue's house and they kiss.

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The title of this episode is a reference to the 1995 Mobb Deep song "Shook Ones, Part II".^[6]

As a child, Maddy loses interest in the idea of working after her mother stops her from participating in beauty pageants. She eventually finds herself in a toxic relationship with Nate, culminating in his attack on her at the carnival. In the present, Rue tells her mother that she is dating Jules. Maddy tries to hide the injuries on her neck, but they are discovered after she passes out at school and a police investigation begins; Maddy's mother presses charges against Nate. Jules gets frustrated when Rue dismisses her situation with Cal. Ali does not believe that Rue's and Jules's relationship will last, scaring Rue. Cassie reconciles with McKay, who apologizes for his behavior at the carnival. Kat is cold toward Ethan, who does not understand why. Kat has a sexual encounter with a clothing store clerk about whom she had previously fantasized. Rue apologizes to Lexi for having been a bad friend and invites her to go roller skating with her and Jules. Cal questions the effects his secret sexuality has had on his children. Maddy meets Nate at a motel. After rollerskating, Jules takes Rue home with her, but cannot sleep.

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The title of this episode is a reference to the 2002 Jay-Z and Beyoncé song " '03 Bonnie & Clyde".^[6]

Growing up, McKay is coached to become a successful football player by his father, who advises him to bottle up his emotions. When he reaches college, he realizes he has little chance of being recruited by a professional team. In the present, Nate is suspended from school and socially ostracized. Nate breaks into Tyler's apartment and coerces him into confessing to choking Maddy. He also blackmails Jules into telling the police that she saw Tyler attack Maddy. Cassie attends a Halloween party with McKay, where he is violently hazed and dry humped^[11] by his fraternity brothers. He then has aggressive sex with Cassie, taking out his anger on her. This leaves her in tears. The next night, Daniel hosts a party. Rue worries about Jules, who is drinking heavily and expresses uncertainty about her relationship. Rue apologizes to Fez for lashing out at him. Kat hooks up with Ethan but ditches him when he visits the bathroom. When Cassie refuses to have sex with Daniel, he insults her. At home, Cassie realizes her period is late. Nate and Maddy arrive at Daniel's party and are applauded by the partygoers. Rue becomes suspicious when she sees Jules's reaction.

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The title of this episode is a reference to the 1999 Dr. Dre and Snoop Dogg song "The Next Episode".

Cassie's parents get divorced when she is in her early teens. After a car crash, her father descends into drug addiction and poverty and abandons their family. She frequently enters exploitative sexual relationships with her peers until she meets McKay. In the present, Rue falls into a depression after Jules grows distant, causing her bladder to shut down. After she and Lexi figure out what Nate did to Jules, Rue asks Fez to intimidate him. He does so, but Nate retaliates by anonymously reporting Fez to the police, forcing Fez and Ashtray to dispose of their stash when the police come to their home. Maddy confronts Kat over her new, assertive persona. Kat ends a cam session with a high-paying client when it makes her uncomfortable. Cassie tells McKay she is pregnant. He is overwhelmed and suggests she get an abortion. Jules visits TC, a friend from her old town, and meets TC's roommate, Anna. Jules and Anna go clubbing, take psychedelics, and share a sexual experience, during which Jules hallucinates about both Nate and Rue. She texts Rue the next morning to tell her that she misses her.

Rue and Jules reconcile as Rue recovers in the hospital after a kidney infection. Nate is unable to sexually perform with Maddy, who confronts him about his sexuality, after which Nate attacks her. Maddy steals the video of Cal and Jules that Nate has in his possession, later watching it in shock. Nate wins his final high-school football game, but Cal criticizes his performance. Nate attempts to fight him but after being subdued, begins to hit himself, leaving Cal shaken. Cassie terminates her pregnancy with her family's support. Fez breaks into Mouse's supplier's house and robs him in order to pay Mouse. At their school's winter formal, Kat seeks out Ethan and apologizes for her behavior. Rue confronts Nate, threatening to expose Cal. Nate taunts her about Jules's loyalty. After spending the night trying to make each other jealous, Nate and Maddy decide to peacefully end their relationship. Jules tells Rue that she is in love with both her and Anna. Rue and Jules decide to run away from their town together, but Rue backs out at the last minute and Jules leaves on a train alone. A heartbroken Rue returns home and relapses, experiencing a vivid, musical hallucination.

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The title of this episode references "Salting the earth", to ruin a conquered land.

After her relapse, an intoxicated Rue meets with Ali at a diner on Christmas Eve, and they talk about their addictions. Rue admits that she willingly relapsed; Ali reminds her that addiction is a disease and emphasizes the importance of committing to a cause greater than herself. Rue attempts to blame Jules for her relapse, but Ali points out that Rue had been saving the pills she took, suggesting that she was never serious about staying clean. He also notes that Rue never officially acknowledged her relationship with Jules. Rue eventually admits that she feels guilty about her treatment of her family, particularly her mother, and that she is suicidal. Ali argues that drugs fundamentally change a person; he reveals that his birthname is Martin and he grew up with an abusive father for whom he harbored deep hatred, only to become violent with his wife after developing a drug addiction, estranging his daughters. Ali tells Rue that a refusal to forgive oneself for one's mistakes is what prevents personal growth, and that he has faith in her ability to improve.

On Christmas Eve, after leaving Rue behind at the train station, Jules attends her first therapy session. She says Rue is the only person she believes loved her for who she truly is, but admits resenting the burden of having to preserve Rue's sobriety by being constantly available to her. Flashbacks reveal that Jules's mother was recovering from addiction during the events of the first season, but was hospitalized as the result of a relapse after overhearing Jules admit she cannot forgive her for abandoning her as a child. Jules's therapist observes that Jules's complicated feelings about Rue closely resemble those she has about her own mother. Jules further confides that she is still in love with "Tyler", the fake online persona Nate used to communicate with her, despite knowing that their relationship is a fantasy. Jules tells her therapist that she is contemplating going off her hormones, specifically her blockers due to her evolving notion of her own femininity, which she believes she has expressed only to please men. Upon returning home, Jules receives a surprise visit from Rue, who says she is on her way to meet Ali. Jules tries to apologize to Rue for leaving her, but an emotional Rue simply wishes Jules a merry Christmas before abruptly leaving. Jules breaks down crying in her bedroom.

As a child, Fez is taken under his grandmother's wing and introduced to the drug trade. A baby Ashtray is abandoned by his addict mother. Fez experiences a traumatic head injury from a crowbar accident. In the present, Ashtray kills Mouse with a hammer. Several weeks later, on New Year's Eve, an intoxicated Rue accompanies Fez and Ashtray to a harrowing drug deal with associates of retired-schoolteacher-turned-dealer Laurie, before attending a large house party. After encountering each other at a convenience store, Nate and Cassie impulsively have sex in a bathroom at the party and are nearly caught by Maddy. Rue takes a spate of drugs with a student named Elliot and nearly overdoses. She reunites with Jules and admits to relapsing the night Jules left her at the train station. The two later confess their feelings for one another and kiss. Fez flatters Lexi and gets her number, then confronts Nate, whom he viciously beats until the other guests stop him.

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The title of this episode is a reference to the 1997 Bob Dylan song "Tryin' to Get to Heaven".

Nate recovers from his beating at the hospital, refusing to tell his father who attacked him. Cassie, who has experienced a depressive episode since her abortion, continues seeing Nate despite knowing it could ruin her friendship with Maddy. Jules becomes insecure about Rue's friendship with Elliot, unaware the two have been regularly taking drugs together. After encountering an intoxicated Rue at their Narcotics Anonymous meeting, Ali drives her home and meets her family. Kat's interest in Ethan begins to wane over her own issues with self-esteem. Cal investigates Nate's assault and pressures Cassie into naming Fez as the attacker. He later confronts Nate, who responds by revealing he knows of his father's secret sexual exploits, including the video of him and Jules.

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The title of this episode is a reference to the 1984 Hall & Oates song "Out of Touch".

As a teenager, Cal is attracted to his friend Derek while dating his future wife, Marsha. Derek reciprocates his feelings, but Marsha's unexpected pregnancy compels Cal to stay with her and hide his sexual orientation. In the present, Jules forgoes her insecurity about Elliot and Rue, becoming friends with Elliot. Rue develops a plan to hide her drug use from Jules and Gia. When she runs out of drugs, she convinces Laurie to give her a large stash, ostensibly for Rue to sell. Ali becomes suspicious of Rue, causing a heated argument that leads them to cut ties. Cassie becomes further isolated due to her obsession with Nate. Lexi channels her frustrations with Cassie and Rue, as well as her own loneliness, into writing a play to stage at school. Cal visits Fez, thinking he has the video of Jules, but Ashtray beats him into admitting his indiscretions. Fez lets him go on the condition that he stops hunting him and keeps Nate away from Rue and Jules. Nate cancels plans with Cassie to rekindle his relationship with Maddy.

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The title of this episode is a reference to the 2000 Robert Rauschenberg painting "Ruminations: Big and Little Bullys".

While by themselves one night, Jules and Elliot kiss. Cassie and Nate's relationship becomes strained after he admits to having resumed talking to Maddy. The Howards host a birthday party for Maddy, where Cassie gets exceedingly drunk and later vomits in the hot tub as Maddy is yelling at Nate for always smooth-talking her back into a relationship. Rue, Jules, and Elliot rob a convenience store for White Claw. Jules questions Rue for drinking, angering Rue and compelling her to go back home. She pops four pills and hallucinates her father in a church, while also seeing Labrinth singing. Cal gets drunk and drives to the gay bar where he first kissed Derek; after getting thrown out, he returns home, drunkenly berates his family for not allowing him to be open about his sexuality, and abruptly decides to leave them. Elliot discloses Rue's ongoing drug use to Jules. Jules is devastated but sleeps with Elliot nonetheless.

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The title of this episode is a reference to the French Surrealists phrase "You Who Cannot See, Think of Those Who Can".

Rue's suitcase of drugs she acquired from Laurie is missing; her mother Leslie, who learned of her relapse from Jules, reveals she threw it out. Rue in turn has a violent meltdown at her mother and sister, as well as Jules and Elliot, who are there for the intervention. On the car ride to rehab, she runs away and goes to Lexi's house; her mother and friends are there for the intervention. Rue reveals Cassie's and Nate's relationship, causing chaos and allowing her to get away. She goes to Fez's place, but he throws her out when she tries stealing his grandmother's medication. She burgles a house, getting cash and jewelry to start paying back Laurie for the drugs. Reeling from withdrawal, Rue narrowly outruns and hides from the police, and reaches Laurie's apartment. Laurie mothers Rue, giving her a bath and pharmaceutical morphine for the pain, but implies she will force Rue to prostitute herself to pay her debts. Rue wakes up early the next morning, sneaks out of the apartment, and returns home.

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The title of this episode is a reference to the 1962 Henry Miller book Stand Still Like the Hummingbird.

Two weeks after returning home, Rue makes progress in recovering from withdrawal, reconciling with Ali in the process. Kat breaks up with Ethan, who confronts her for being dishonest and absent in their relationship. Cassie and Nate struggle with their secret being out and argue with their mothers. Cassie's stress makes Lexi wonder how her play will be received. Fez is housing Faye, the girlfriend of his associate Custer, whom he hasn't seen since the deal with Laurie; Custer privately meets Faye and reveals he is a police informant working to bring down Fez and Ashtray for Mouse's murder. Nate goes to Maddy's house and forces her at gunpoint to give up the disc containing the video of Cal and Jules. He then gives Jules the disc, apologizing for his past behavior; the two admit the feelings they expressed to each other by text message the previous year were genuine. Leslie learns no inpatient facility has room for Rue and breaks down, fearing Rue will kill herself without treatment.

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The title of this episode is a reference to Federico García Lorca's "The Martyrdom".

Jules destroys the disc Nate gave her. Leslie tells Rue she is done dealing with her drug addiction and plans to focus on Gia. Maddy wishes to leave East Highland after the end of the school year, feeling there is nothing to keep her there. Lexi's play, Our Life, is performed for East Highland's students, parents, and faculty; the students quickly realize the play is based on their lives. The play shows various significant events from Lexi's perspective, such as Rue's father's wake, Cassie's puberty, Rue's and Lexi's friendship, Cassie and Maddy's friendship, and Maddy and Nate's relationship. Fez fails to make it to the play despite promising Lexi he would be there. Ethan, playing Nate, performs a homoerotic rendition of "Holding Out for a Hero" with other male students; an offended Nate storms out of the play and angrily breaks up with Cassie, who is enraged.

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The title of this episode is a reference to Antonin Artaud's 1938 book The Theatre and Its Double.

Cassie disrupts the play when she rushes the stage and berates Lexi, only to be chased backstage and attacked by Maddy. Lexi finishes her play with the crew's and audience's support. While getting ready to attend Lexi's play, Fez is visited by Custer, who is wearing a wire. Ashtray realizes Custer is a police informant and fatally stabs him, while Fez destroys his phone. Police storm the compound; Ashtray locks himself in the bathroom and engages in a shootout with the police. Fez is shot and wounded during the altercation and later arrested, while Ashtray is fatally wounded. Nate confronts Cal with a flash drive containing all of Cal's explicit videos, before the police, tipped off by Nate, come to arrest Cal. In the aftermath of their brawl, Cassie confesses to Maddy that Nate dumped her, to which she responds that this is just the beginning of what Cassie will have to endure. After the play, Jules tells Rue that she loves and misses her, to which Rue responds by kissing her on the head before leaving in silence; Jules cries alone. Rue narrates that she stayed clean for the rest of the school year and is cautiously optimistic about the future.

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The title of this episode is a reference to André Breton's "Mad Love".

Five years later, Rue's friend group has splintered. Lexi is a production assistant on a Warner Bros. soap opera; Maddy is an actors' talent manager; Nate and Cassie are engaged, with Cassie pursuing fame as an erotic influencer; and Rue is a drug mule for Laurie, to whom she owes an enormous debt. Fleeing across the Mexico–United States border, Rue encounters a devoutly Christian family. Reflecting upon her encounter with the family, and with some prodding from her sponsor, Ali, she reconsiders faith in a higher power—her "third step". Lexi tells Rue that Jules has become a sugar baby in New York. Cassie decides to start selling erotic content on OnlyFans to help pay for her dream wedding. Nate, trying to resurrect his father's construction company, dislikes the idea, but relents after Cassie agrees to hide her face. Rue delivers drugs to a party at strip-club mogul Alamo's mansion. Rue asks Alamo for a job, but when one of Alamo's strippers, Tish, overdoses on a fentanyl-laced pill, Alamo plays a game of William Tell, shooting an apple off of Rue's head, earning Alamo's trust.

Maddy's career as a talent manager stalls after the COVID-19 pandemic, leading her to manage influencers until she is forced to drop a client who becomes too close to one of her boss's actors. Alamo recruits Rue to help cover up Tish's death and manage the floor at a strip club. Laurie and her dealers hurl racist insults at him, prompting Alamo to retaliate by sending a pig to her house. Rue has a brief relationship with a stripper named Angel, who is shaken by Tish's disappearance. When Rue reveals the truth, Angel spirals; with Alamo's approval, Rue stages an intervention and takes her to rehab. Cassie asks Maddy to help build her online presence, and she agrees. Indebted to loan sharks, Nate tries to recruit investors from his neighborhood, but one withdraws after discovering Cassie's OnlyFans and learning about Nate's finances. Nate forces Cassie to delete the account. Later, Rue visits Jules at her penthouse. Their conversation is marked by mutual resentment and sexual tension; Jules chides Rue for judging her work before inviting her to take a bath with her.

While in art school, Jules is introduced to sugaring by her roommate. She becomes the paid mistress of plastic surgeon Ellis, who provides her with an apartment and the resources to quit school and focus on painting, but who engages her in extreme BDSM. Meanwhile, Rue starts trafficking guns for Alamo while pondering "going straight". Tensions rise when Laurie retaliates against Alamo by releasing a pig at his strip club. He plans to get revenge by killing her pet cockatoo, Paladin. Rue, Jules, and Maddy attend Cassie and Nate's gaudy wedding, where Nate's loan shark, Naz, publicly intimidates the couple. Jules shares conciliatory moments with Nate and Cal, while Maddy is overcome with emotion and leaves. Rue departs to pick up drugs from Laurie to cover for Alamo's henchman Bishop poisoning Paladin. Cassie breaks down and injures Nate; they reconcile briefly before Naz and a thug attack Nate at home, beating him and cutting off his toe. Rue is stopped by a DEA officer.

To avoid a lengthy prison sentence, Rue becomes a DEA mole for an investigation into Laurie's drug ring, but Alamo assumes that he will never do business with Laurie again. When Rue offers to set up a fake buy in Mexico, Alamo becomes suspicious of her motives. Cassie leaves Nate, moves in near Lexi, and resumes her OnlyFans career with Maddy as manager. Nate's last-ditch attempt to gain funding for his development is denied, and he has an emotional breakdown in public. Lexi hires Jules to paint a picture for her soap opera. Jules' piece contains nudity, which the show's producers cannot broadcast. Jules is forced to cover up the nudity, offending her and hurting Lexi's standing with her boss. Maddy has Cassie feign romantic interest to a social media star at his house to promote her OnlyFans. Rue expresses concern to Angel's replacement, Kitty, after learning that Angel fled rehab and seeing Kitty have violent group sex in a private room. Magick, another stripper, overhears and nearly blows Rue's cover, but Laurie's squad raids the club, shoots the club manager, and robs the safe.