Young Cameron 'Cam' Cade [Tyriq Withers] watches his favorite football team, the San Antonio Saviors, win the league championship. His joy turns to distress when his quarterback idol Isaiah White [Marlon Wayans] suffers a violent, possibly career-ending injury while scoring the winning touchdown. Cam's father tells him that real men are willing to make sacrifices.
Years later, Cam has become a rising star. Encouraged by his family and girlfriend, he trains for the league combine. While practicing late on an empty field, Cam is attacked by someone in a goat costume, resulting in a head injury that threatens his career.
Motivated by his agent, [Tim Heidecker], Cam plans to attend the combine to pursue the Saviors' quarterback role, despite risking permanent brain damage if he sustains another injury. While overstimulated due to his concussion, Cam lashes out at his brother and Tim, ultimately refusing to participate. Tom later reveals that Isaiah is considering retirement and has offered to train Cam for a week at a remote desert compound to prove himself a worthy successor. Cam accepts and travels there, facing crazed Isaiah fans led by Marjorie [Naomi Grossman], who try to intimidate him out of replacing their hero.
At the compound, Isaiah puts Cam through disturbing challenges, including a practice drill where a football machine repeatedly hits a player in the face. Cam secretly receives shots of Isaiah's blood, which he is led to believe is an energy booster, and experiences frequent hallucinations of masked figures, which he attributes to the concussion.
While in a sauna, Cam is attacked by Marjorie and overpowers her. Isaiah arrives and emotionlessly kills her, to Cam's consternation. As Cam tries to leave, Isaiah's wife Elsie [Julia Fox] apologizes and seduces him. Cam wakes the next morning to Isaiah holding him at gunpoint, demanding to know if Cam and Elsie slept together. Isaiah ridicules Cam for feeling guilty about cheating on his girlfriend, saying winners are remorseless.
Elsie invites Cam to a secret party to meet the Saviors' owners. Upon arrival, Marco, the team doctor, whispers to Cam to "run" before leaving. The owners offer Cam a strange red liquid, which he drinks, unaware that it is Isaiah's blood. A disoriented Cam finds Marco's severed head in a plastic-lined room. Elsie comforts him as he loses consciousness. Cam later wakes up in an ice bath at Isaiah's compound, connected to an IV of Isaiah's blood. He rips out the IV and grabs a jagged trophy, aiming to kill Isaiah and escape.
Cam finds Isaiah watching a video of cheering fans. Isaiah reveals he is part of a line of manufactured "Greatest of All Time" (G.O.A.T.) players who gain enhanced abilities from ritual blood transferred down a lineage. Isaiah tells Cam they must fight to the death with one G.O.A.T. transfusion victor. After a struggle, Cam bludgeons Isaiah to death with a helmet.
Cam leaves the room and steps onto a football field, where he finds Elsie, the Saviors' owners, and Tim, all wearing animal masks. They present him with a contract to sign, revealing that Cam's father arranged for him to be the next G.O.A.T. They explain that the earlier masked attack was orchestrated to lead Cam to the Saviors. Cam refuses to sign the contract and, in a violent outburst, kills all the owners, Elsie, and the masked attacker—who is revealed to be Isaiah and Cam's trainer, Malek—using a hammer and sword. However, he spares Tom, who is subsequently dragged into a pentagram and destroyed by an unseen force.
Outside the compound, a bloodied Cam walks past masked cheerleaders and into the desert.
