Endgame is set after some sort of apocalyptic disaster (though we never learn the details). Hamm, his servant Clov, his father Nagg, and his mother Nell are trapped together in Hamm's home.
The play opens on a bare stage in gray light. It is a room of Hamm's house. To the left are two trash bins covered in sheets. In center stage is Hamm, seated in a wheelchair and covered in a sheet. (He's also blind.) At the back of the room are two windows, and to the left is a kitchen. The first character to appear is Hamm's servant, Clov, who goes through a long routine – he opens the curtains on the windows and pulls the sheets off of all the other characters. He then goes to his kitchen.
When Hamm awakens, he calls for Clov, and the two of them discuss the possibility of things ending. At one point, Hamm asks why Clov does not leave him, and Clov says that there is no one else. Later, Hamm again asks why Clov doesn't kill him, and Clov says that he does not know the combination to the cupboard. After a while, Hamm's parents, Nagg and Nell, emerge from their trash bins. Nagg wants Nell to kiss him and to scratch him, but Nell is less enthusiastic. Nagg tells a long joke in an attempt to cheer Nell up, but she doesn't laugh. Discouraged, they both return to their trash bins.
Hamm calls again for Clov so that Clov can take him for a tour around the room in Hamm's wheelchair. As Clov returns Hamm to his original spot, Hamm becomes obsessed with being in the exact center of the room.
Hamm then demands that Clov look out the window and report what he sees, which is nothing. Clov says that he is sick of their farce, day after day. Hamm, for his part, worries that the two of them are beginning to mean something. While Hamm is making a speech, Clov discovers that he has a flea. Both of them worry that the flea might have babies and start up the world from scratch again. Clov kills it dramatically with a can of insecticide.
The two of them continue their bickering. Hamm tells Clov that Clov can't leave him, and Clov concedes that this is true. Later, Hamm asks Clov to kill him, but Clov says that he can't. Instead, Hamm sends Clov to get a stuffed dog that Clov is making for him. Hamm wants Clov to set the dog beside his wheelchair to make it seem as though the dog is gazing up at him imploringly. Clov does so, and then accuses Hamm of not helping an old woman named Mother Pegg, who needed oil for her lamp. Hamm tries to deny this.
Clov wonders why he never refuses Hamm's orders, and Hamm says that it is because Clov is unable to. Hamm recalls a madman that he knew, who thought that the entire world was ashes. Hamm doesn't think this man's case is unusual.
Once again, Clov threatens to leave. Hamm and Clov get into a long debate about how Hamm would know if Clov left or if Clov died in the kitchen. Clov decides that if he leaves, he will set an alarm clock so that Hamm will be certain of what Clov has done.
Hamm has Clov awaken Nagg, so that Nagg will listen to his story. Nagg agrees to listen if he gets a sugarplum. With many stops and starts, Hamm recounts what is probably the story of how he obtained Clov from Clov's father, who was one of Hamm's subjects before the end of the world. At the end of the story, Hamm tells Nagg that there are no more sugarplums. Nagg curses him at length, and returns to his bin.
Hamm makes Clov bring him his dog again. After he does so, Clov begins to tidy things up around the room. When Hamm asks what he is doing, Clov says that he is trying to put things in order, because order is his dream. Hamm demands that Clov check on his parents, and they learn that his mother, Nell, is dead, and Nagg is in his trash bin crying. Neither Hamm nor Clov show any sign of sympathy for Nagg.
Hamm asks Clov if he has ever been happy. Clov says no. Hamm makes Clov bring him under the window because he wants to feel the light, but he realizes that there is none. When he gets back to the center of the room, Hamm asks Clov to kiss him, but Clov refuses. Hamm makes a speech in which he talks about how the end happened right in the beginning and yet they continued on. Hamm forces Clov to check the windows again for action outside. Clov becomes extremely frustrated with him, and when Hamm again asks for his stuffed dog, Clov rushes over and hits him with it.
Clov, looking out the window, thinks that he sees a boy, and decides to go find him. Hamm says that he doesn't need Clov anymore, but asks him for a few parting words for Hamm to hold in his heart. Clov recalls all the promises of happiness people made to him when he was growing up, and then thinks how happy he will be when he finally falls. Clov goes to the kitchen. Hamm calls for him, but he does not respond. Hamm calls for his father, but he does not respond either. Hamm decides that this is good, and casts away his few possessions. He makes a short speech on the nature of ending and then covers his face with his handkerchief. Clov stands in the doorway the entire time, dressed to go, but unmoving.