Cassius "Cash" Green lives in his uncle Sergio's garage with his artist girlfriend, Detroit. Struggling to pay rent, he gets a job as a telemarketer for RegalView. Cash has trouble with customers until Langston, an older co-worker, teaches him to use his "white voice" and adopt a blithe, affluent persona on calls, at which Cash excels.
Cash's coworker Squeeze forms a union and recruits Cash, Detroit, and their friend Sal. When Cash participates in a protest, he expects to be fired but is instead promoted to an elite Power Caller position.
In the luxurious Power Caller suite, the lead Power Caller, Mr. _______,[a] tells Cash to always use his white voice. He learns that RegalView secretly sells military arms as well as cheap labor from the megacorporation WorryFree, through which employees sign lifetime contracts to work and be housed in factories, which many condemn as slave labor.
Though Cash is initially uncomfortable with the job, he is celebrated at work and can now afford a new apartment and a flashy new car, and pay off Sergio's house (in the process keeping him from joining WorryFree). Through his newfound success, he initially improves his relationship with Detroit and boosts his sex life significantly.
Cash stops participating in the union push and Detroit quits her RegalView job to avoid conflicting loyalties between the two, while secretly participating in the Left Eye Faction, an anti-WorryFree activist group. She eventually breaks up with Cash, arguing that his immoral job has changed him, while he insists he has the right to be proud of his success.
When Cash is escorted through the union's picket line one morning, a picketer wounds him with a can of soda. Footage of the incident becomes an Internet meme; the thrower profits from it herself, even signing a sponsorship with the soda brand she threw.
Cash then attends Detroit's art exhibit and artistic performance uninvited, at which she uses a white voice of her own. He tries to stop the event, but that only motivates Detroit to kick him out; afterwards, she has everything but sex with Squeeze.
Cash is invited to a debaucherous party with WorryFree CEO Steve Lift, where he is goaded into rapping for the predominantly white guests. Later, in a private meeting, Lift offers Cash a powdered substance which Cash snorts, believing it is cocaine.
Looking for the bathroom, Cash discovers a shackled half-horse, half-human hybrids¡ who begs him for help. Lift explains that WorryFree plans to make their workers stronger, more obedient, and thus more profitable by transforming them into hybrid "Equisapiens" through snorting a gene-modifying powder. Cash fears that he just ingested the substance, but Lift assures him it was cocaine. Cash refuses an offer of $100 million to become an Equisapien for five years to act as a false revolutionary figure to keep the employees in line.
Cash discovers he dropped his phone when he encountered the Equisapiens, who recorded a plea for help and sent it to Detroit. Taking advantage of his infamy as a meme, Cash appears on the extremely popular television show I Got the Shit Kicked Out of Me, enduring humiliations and beatings to share the video, to spread the word about WorryFree's cruelty. The plan backfires: Equisapiens are hailed as a groundbreaking scientific advancement, a cult of personality worshipping Lift develops, and WorryFree's stock price reaches an all-time high.
Cash apologizes to Squeeze, Sal, and Detroit, and rallies the union in a final stand against RegalView. He uses a security code from the Equisapien's video to break into Lift's home. He goes to the picket line, where the police start a riot and detain Cash, but the Equisapiens overpower them and free him.
Detroit and Cash reconcile and later move back into Sergio's garage. Cash suddenly starts to grow horse nostrils. Later, fully transformed, he leads a mob of Equisapiens to Lift's house and breaks down the door.
