Wearing Elizabethan costumes on a blank stage, Rosencrantz and Guildenstern are tossing coins, all of which land 'heads.' Rosencrantz is unperturbed by the improbable odds but Guildenstern grows disturbed, demanding Rosencrantz think through potential meanings of the unlikely situation. They realize they can't remember a past before tossing coins and have only vague recollection of being called by royal summons. The Tragedians march onstage lead by the Player, who sees Rosencrantz and Guildenstern as a potential audience and tries to entice them into buying a performance with the chance to sodomize the lowliest tragedian, Alfred. Guildenstern is appalled but the Player maintains that people only go to the theater for crude entertainment full of "blood, love, and rhetoric" (and mostly blood). The Player accepts and loses two futile bets to Guildenstern and agrees to pay with a play. Rosencrantz extracts a coin from under the Player's foot, sees it fell on tails, and, suddenly, the lighting shifts the scene to Elsinore Castle.
A disheveled Hamlet and Ophelia run on stage for a brief, mute appearance. Then Claudius and Gertrude enter, welcoming Rosencrantz and Guildenstern and explaining they've been sent for to uncover the cause of Hamlet's recent transformation. Rosencrantz and Guildenstern agree to do so, then, alone on stage, lament the absurd incomprehensibility of their situation. Perplexed by what action to take, they stay passive. The sight of Hamlet prompts them to practice acting in character, but they muddle their names. Just as Guildenstern decides they're "marked," Hamlet walks on taunting Polonius. When Hamlet notices Rosencrantz and Guildenstern, he greets them warmly but can't tell them apart. The lights black out and rise on Act Two, where Rosencrantz and Guildenstern are still talking with Hamlet, who explains he's only mad when the wind blows north. Alone, Guildenstern tries to be optimistic but Rosencrantz insists they made no headway with Hamlet, who made them "look ridiculous." They try to figure out which direction's south and wonder if anyone will enter. Guildenstern alludes to an "order" of which they are a part.
Hamlet enters with the Tragedians, who he's booked to play the next night, then exits. The Player is cold towards Rosencrantz and Guildenstern, who left midway through the Tragedians' performance, humiliating them beyond measure. An actor's whole existence, the Player explains, depends on being watched. Guildenstern asks desperately for acting advice to help his and Rosencrantz' efforts with Hamlet. "Act natural," the Player says, and tells them there's no truth, only assumptions. He exits. Hamlet, Claudius, Gertrude, and Ophelia enter briefly and Rosencrantz and Guildenstern assure Gertrude they're making progress with Hamlet.
The Tragedians return to rehearse their play, whose plot turns out to be Hamlet's, including Rosencrantz's and Guildenstern's deaths played by actors wearing Rosencrantz and Guildenstern's clothes. Rosencrantz and Guildenstern are uncomprehending. Entrances by Ophelia, Hamlet, Claudius, and Polonius interrupt the Tragedians' play. The Player calls the play "a slaughterhouse," bringing out the actors' "best." Guildenstern criticizes spectacular stage deaths, insisting death is simply "a man failing to reappear." The lights blackout. The sun rises on Rosencrantz and Guildenstern alone.
Claudius enters briefly and tells Rosencrantz and Guildenstern to find Hamlet and Polonius' corpse (Hamlet murdered him) but the two procrastinate and, when a scornful Hamlet enters, are unable to make him obey them. Alone, Rosencrantz and Guildenstern despair. Hamlet eventually returns and promises to go with them to England.
Act Three opens on Rosencrantz, Guildenstern, and Hamlet on the boat to England. While preparing their speech to the King of England, Rosencrantz and Guildenstern read the letter Claudius gave them and realize it orders Hamlet's death. They're at first horrified and wonder if they should intervene, but eventually rationalize passivity and feel better. While they sleep, Hamlet steals, reads, and replaces the letter with another.
The Tragedians' appear on the ship as stowaways, pirates attack, and Hamlet goes missing, distressing Rosencrantz and Guildenstern. Reviewing their plan, they now discover that the letter orders their own execution. They're indignant, then despairing. Infuriated by the Player's calm claims to understand death, Guildenstern stabs him and the Player falls and dies. But the dagger turns out to be fake and the Player stands up, alive and smug, having convinced Guildenstern with the very sort of acted death Guildenstern claims isn't convincing. The Player and Tragedians' gleefully act out various deaths. Lights fade on them. Alone, Rosencrantz and Guildenstern's exasperation at death gives way to resolved acceptance. Rosencrantz disappears, then Guildenstern does.
Lights rise on the corpse-strewn end of Hamlet. An ambassador reports that Rosencrantz and Guildenstern are dead and the lights fade out as Horatio promises to tell the tragedy's story.