Act I opens with Rosencrantz (Ros) flipping a coin that has landed heads up over ninety times in a row. Ros and Guildenstern (Guil) are betting on the flip of the coin. Ros feels slightly guilty for taking so much money from his friend, but is not as tuned into the oddness of what is occurring. Guil is trying to understand why mathematical laws of probability seem to have failed, and attempts to get Ros to be as bothered by their situation as he is. While they talk, Guil and then Ros remember that a messenger awoke them that morning and that they are supposed to be on some sort of important official business.
A troupe of actors arrives led by a character called "the Player." The Player offers to perform any sort of tragedy for Ros and Guil for a fee. He shows off the range of his fellow players (actors), but when he offers to perform the Rape of the Sabine Women, Guil is taken aback and slaps him. Guil accuses the Player of being a pornographer.
Guil challenges the Player to a coin tossing game, and, predictably, the Player loses. He then bets the Player that the year of his birth doubled is an even number. The Player again takes the bet before realizing that any number doubled is an even number. They continue to bicker until the Player walks off, and the scene is interrupted by a scene from Hamlet.
King Claudius (Hamlet's uncle and new stepfather) and Queen Gertrude (Hamlet's mother) ask Ros and Guil to find Hamlet, cheer him up, and figure out what is troubling him. After they leave, Ros and Guil feel directionless and wish to be at home. They play a word game called "questions" and banter back and forth.
When they see Hamlet walk across the stage with a book, they decide to role-play: Guil as Hamlet and Ros as himself. Ros questions Guil/Hamlet, and they determine that his trouble is related to the fact that his father died, and his uncle (Claudius) quickly married Hamlet's mother (Gertrude), making him king. They are interrupted by Hamlet, who greets his friends warmly. The act ends with the three of them walking off the stage, arm-in-arm.
Act II opens with the continuation of the conversation from Act I. Hamlet tells his friends that he is not completely crazy, but afterward Ros and Guil think that they've failed to figure out what is wrong with Hamlet. Hamlet hangs around and asks the Player to put on a play called The Murder of Gonzago, with a special added part that Hamlet will write.
The Player, Ros, and Guil start chatting. When Guil keeps trying to clarify what is going on, the Player tells him that he can't constantly be questioning his situation – that sometimes he just as he to relax and act naturally (a.k.a. chill out). The Player proceeds to tell Ros and Guil about how Hamlet wants the actors to put on a play about a king and queen. Fortunately, the play Hamlet desires hits on all the actors' strengths (blood, love, and rhetoric).
Since the Player has brought Hamlet up, Ros and Guil begin to discuss what is going on with Hamlet. They think that Hamlet is still sane, and the Player tells them that Claudius thinks Hamlet is in love with Ophelia. The Player and Guil move to a discussion of death.
Then Claudius and Gertrude pass through the play. Claudius mentions that he has set up a situation where Hamlet will run into Ophelia (his love interest, sort of) and it will seem like an accident.
Rosencrantz and Guildenstern watch the dress rehearsal of the tragedians' (the actors) play. It depicts events that have or will soon come to pass. First, the original King is poisoned by his brother, and the brother then marries the widowed Queen and usurps the throne. (This sounds a lot like what happened with Claudius and Gertrude).
Hamlet and Ophelia pass through the rehearsal. Ophelia is crying, and Hamlet is acting hysterical. He suggests that either the King or Queen will die. After Hamlet leaves, Claudius enters and tells Ophelia that Hamlet is sane and that he does not love her. He decides to send Hamlet to England.
The dress rehearsal resumes with the uncle and the widowed Queen entangled in a love affair. Ros is upset by the sordidness of the scene, and argues that this is not what people want to see. The Player asks him what he would prefer, and Ros says that he wants a simple story with a beginning, middle, and end. The Player then asks Guil what he expects out of a play, and Guil says that he would prefer art to reflect life.
In the dress rehearsal, the Prince confronts the Queen, and then stabs his uncle's aide. The play then depicts the Prince's banishment to England, accompanied by his two friends (the actors that play the roles corresponding to Ros and Guil in real life). Though the two friends die in this play, Ros and Guil fail to recognize themselves or their fate. The Player and Guil argue about whether or not actors can portray death.
Night passes. When the sun rises, Ros and Guil are lying on their backs in the same positions as the actors who had played them in the tragedians' rehearsal. The events predicted in the rehearsal begin to occur. Hamlet stabs Polonius (King Claudius's aide). Claudius asks Ros and Guil to bring Polonius's body to a chapel, and to bring Hamlet to him. They see Hamlet dragging Polonius's body, but fail to react. It is determined that Ros and Guil will take Hamlet to England, and Hamlet willingly submits. The act ends with Ros thinking that anything could happen.
Act III opens with Ros and Guil in darkness. They are on a boat at sea, sailing to England. They worry about whether or not they are alive, where they are, and what they are doing. They bicker about what they will do when they get to England, and act out a scenario where they meet the King of England. At the end of the scenario, they open the letter they have been given to find that it commands Hamlet's death. They rationalize not doing anything (a.k.a. allowing Hamlet's death), and decide that they are wrapped up in matters beyond their control.
When Ros and Guil sleep, Hamlet edits the letter so that it commands their deaths and not his own. The next morning, Ros and Guil find the tragedians hiding in some barrels on the ship. Claudius did not like their play, and they had to flee. Pirates attack the boat, and everyone hides in barrels. The stage goes dark and the barrel in which Hamlet is hiding disappears.
Ros and Guil again lament their condition. This time Guil is more worried than Ros. They again play out what will happen when they meet the King of England, but when they reopen the letter they've been entrusted with, they find that it condemns them, and not Hamlet, to death. The Player rallies the tragedians, who encircle Ros and Guil.
Guil derides the tragedians' acted deaths, which he claims are nothing like real death, which is the ultimate negative. Guil is ambiguous, but what he means is that death is something that is absolutely impossible to think about or conceive of: it is nothingness. If life is positive, then death is the ultimate negative.
Guil pulls a dagger from the Player's belt and stabs him. The Player appears to die while Guil and Ros watch. Yet a moment later, the tragedians applaud, and the Player rises again to reveal that Guil stabbed him with a trick dagger. The tragedians act out all sorts of deaths, and then the stage goes dark, leaving only Ros and Guil.
Ros wants some justification for their being condemned to death, but then he gives up and says that he is relieved. He disappears. Guil recalls the messenger that woke them, and wonders if there was a way out of their situation that they had overlooked. He disappears with the lines, "Well, we'll know better next time. Now you see me, now you—" (3.347).
The lights go up on the closing scene of Hamlet with dead bodies strewn everywhere. An ambassador from England announces that Rosencrantz and Guildenstern are dead. Horatio, a friend of Hamlet and a character in Shakespeare's Hamlet, delivers a speech asking for all of the bodies to be put high on a stage, and claims that he can truly relate the events that took place and led to all of these deaths. Yet as Horatio is speaking, the music starts and the stage is enveloped in darkness before he finishes.