A decade after the events of Clerks, thirty two-year-old Dante Hicks (Brian OHalloran) is still a disgruntled employee at the Quick Stop convenience store. He arrives for another day of work, only to discover, when he opens the security shutters, that the store is on fire. Randal Graves (Jeff Anderson), Dante's long-time best friend and Quick Stop colleague, had left the coffee pot on the night before. As a result of the Quick Stop's destruction, the two men begin working at a Mooby's fast food restaurant.
After working at Mooby's for nearly a year, Dante is planning to move from New Jersey to Florida with his blonde, bony and wealthy fiancée, Emma (Jennifer Schwalbach Smith). Jay and Silent Bob (Jason Mewes and Kevin Smith) have followed Dante and Randal throughout their adventures, and now loiter outside of Mooby's. Though they no longer use drugs (after being arrested, sent to rehab, and supposedly becoming born-again Christians), they continue to sell them and perform their typical antics in the parking lot.
It is Dante's last day before moving, which inspires Randal to give him a "memorable sendoff" and secretly book a donkey show to perform in the restaurant after closing time. Randal takes great satisfaction in manipulating and shocking his 19-year-old co-worker, Elias (Trevor Fehrman), a hopelessly geeky conservative Christian and obsessive fan of Transformers and the Lord of the Rings trilogy. Randal holds nothing but contempt for both franchises ("There's only one Return, and it ain't of the King; it's of the Jedi"), and taunts a customer who shares Elias' manic admiration of the LOTR series until said customer vomits in disgust.
Dante, meanwhile, has become good friends with their manager, Becky Scott (Rosario Dawson), and the two had a drunken one-night stand several weeks before. Becky is aware that Dante is engaged and moving away and is visibly rattled by it, though she treats the subject casually in conversation. While working the counter, Dante and Randal are forced to wait on a former high school rival, Lance Dowds (Jason Lee), now a millionaire from launching a successful website. While Randal recounts Lance's humiliating initiation experience in freshman year which resulted in Lance being nicknamed "Pickle-fucker," he is still angered by Lance's condescending remarks towards him and Dante. After Lance leaves, Randal convinces Dante to blow off work with him and go ride the go-karts at a local fun center (which Randal claims clears his head). Upon their return, they find the restaurant understaffed and full of customers. While preparing food, Randal launches into a rant and angers two African-American customers (Wanda Sykes and Earthquake) when he incorporates the slur "porch monkey" into his speech. Randal initially refuses to believe it is a racial slur, as he did not know its real definition, and because his grandmother had used it as a "term of endearment" for him during his childhood (he initially did not consider his grandmother to be a racist, though he remembers her referring to a broken beer bottle as a "nigger knife"). Randal vows to reclaim the phrase and give it a more positive meaning.
While Randal manages to hire "Kinky Kelly and the Sexy Stud" to perform the donkey show for Dante that night, Dante becomes torn between his mainstream fiancée, Emma, whom he cares for but has little in common with, and his increasing feelings for Becky. When asked by Becky if he has any fear of marriage, he admits he is scared of his wedding reception because he cannot dance. Becky enthusiastically takes him to the roof and gives him a dance lesson (as The Jackson 5's "ABC" blasts from Jay and Silent Bob's boom box, causing everyone in the restaurant and parking lot to dance as well). Overwhelmed, Dante confesses his love to Becky and is stunned when she reveals that she is pregnant as a result of their one-night stand.
A shocked Dante reveals to Randal that Becky is pregnant with his child, and that she does not want an abortion. Randal is taken aback, but swears not to tell anyone, as Becky had already sworn Dante to secrecy. However, Randal ruins this moments later by congratulating Becky on her pregnancy ('May your first child be a masculine child!"). Becky is furious at Dante for blabbing the secret and lividly drives off. Dante erupts in rage and attempts to punch Randal, who panics inwardly when he sees the Kinky Kelly van enter the parking lot. Randal frantically escorts Dante to his car, telling him to follow Becky and talk to her for an hour. Once Dante leaves, Randal speaks with the gruff-looking driver of the Kinky Kelly van (Zak Knutson), and gives him an hour to set up the show equipment in the restaurant. Meanwhile, Becky and Dante drive around separately, thinking over their situation. Becky pauses in front of a women's care clinic, while Dante is waved at by a little girl (Harley Quinn Smith) through a restaurant window, leading him to contemplate fatherhood.
Dante arrives back at Mooby's, which is emitting smoke from its windows. Dante panics and calls the fire department, only to realize the smoke is from a smoke machine being used for the donkey show. Though shocked by Randal's choice of a farewell gift, Dante is drawn into the show's audience (Randal, Jay, Silent Bob, and a very drunk/stoned Elias). As the show begins, their hopes of seeing an attractive woman slowly disappear. Kinky Kelly, who was assumed to be the female exotic dancer, is actually the name of the donkey, while the Sexy Stud is in fact the burly, tattooed man who had driven the trailer. As the Stud prepares to perform an array of explicit acts on Kelly, Becky returns to the restaurant. Dante again confesses his love for her, and she eventually admits that she cares for him too. Dante's fiancée, Emma, comes to Mooby's to surprise Dante, only to see him kissing Becky. She angrily throws her engagement ring at Becky and leaves in tears.
The fire department arrives, responding to Dante's earlier call. With the donkey show in full swing, most of the attendants drunk, and Randal having spelled out "PORCH MONKEY 4 LIFE" on the back of his shirt with masking tape, everyone but Becky is arrested. In their jail cell, Dante gets into a heated argument with Randal, blaming him for ruining his life. Randal becomes indignant and reveals how upset he was about having his best friend move away. They finally admit how much they care about their friendship, and Randal suggests they get back their good old days at the Quick Stop by re-opening it themselves. Jay and Silent Bob agree to lend them money for the endeavor, on the condition that they can hang out in front of the store whenever they want. They are released from jail shortly after, since (as the Sexy Stud had assured them) you cannot be imprisoned for watching an inter-species sex act.
Dante finally decides to start a family life with Becky and proposes to her at the Mooby's drive-thru window. She, Dante, and Randal work on fixing up the charred Quick Stop, and hire Elias to work Randal's old job at the adjacent RC Video store. The film ends with a content Dante and Randal working the counter at the rehabilitated Quick Stop convenience, happy to be in control of their lives at last.