The setting of the film is a tiny town on the outskirts of "The Zone", a wilderness area which has been cordoned off by the government. The film's main character, the Stalker, works as a guide to bring people in and out of the Zone, to a room which is said to grant "the deepest, innermost" wishes. Residual effects of an unnamed previous occurrence have transformed an otherwise mundane rural area scattered with ruined buildings into an area where the normal laws of physics no longer apply.
The film begins with the Stalker in his home with his wife and daughter. His wife emotionally urges him not to leave her again to go into the Zone due to the legal consequences, but he ignores her pleas. The Stalker goes to a bar where he meets the Writer and the Professor, who will be his clients on his next trip into the Zone. Writer and Professor are not identified by namethe Stalker prefers to refer to them in this way. The three of them evade the military blockade that guards the Zone using an 88" Series II Land-Roverattracting gunfire from the guards as they goand then ride into the heart of the Zone on a railway handcar. The camera follows their passage from urban setting to rural, and from the darkness required for their infiltration of the zone, to light.
Once in the Zone, the Stalker tells the others that they must do exactly as he says to survive the dangers that are all around them. Although the Stalker describes extreme danger at all times, no harm comes to any of the three men; there is a tension between disbelief of the need for his elaborate precautions, and the possibility that they are necessary. The Stalker tests various routes by throwing metal nuts tied with strips of cloth ahead of him before walking into a new area. The Zone usually appears peaceful and harmless, with no visible dangers anywhereWriter is skeptical that there is any real danger, while Professor generally follows the Stalker's advice.
Much of the film focuses on the trip through the dangerous Zone, and the philosophical discussions which the characters share about their reasons for wanting to visit the room. Writer appears concerned that he is losing his inspiration, Professor apparently hopes to win a Nobel prize, the Stalkerwho explains that he never visits the room himselfquotes from the New Testament and bemoans the loss of faith in society. Throughout the film, the Stalker refers to a previous Stalker, named "Porcupine," who led his poet brother to death in the Zone, won the lottery, and then hanged himself. The implication is that our "deepest, innermost desires" are opaque even to ourselves, and the overt desire to win the lottery was coupled with the covert and unexpressed - perhaps unconscious - desire that his brother dies - and when Porcupine realized this, he killed himself to expiate his guilt. When the Writer confronts the Stalker about his knowledge of the Zone and the room, he states that it all comes from Porcupine.
They first walk through meadows, and then into a tunnel which the Stalker calls "the meat grinder". In one of the decayed buildings, a phone inexplicably begins to ring. Writer answers and says that this is not the clinic and hangs up. Professor then uses the phone to call a colleague. In the resultant conversation, he reveals some of his true motives for having come to the room. He has brought a bomb with him, and intends to destroy the room out of fear that it could be used for personal gain by evil men. The three men fight verbally and physically; the Professor backs down from his plan to destroy the room. Their journey ends when they arrive at the entrance of the room. A long take, with the camera in the room, leaves the men sitting outside the room, and does not clarify whether they ever enter. Rain begins to fall from a dark sky where a ceiling once was, into the ruined building, and the rainstorm gradually fades away, all in one shot.
The next scene shows the Stalker, Writer, and Professor back in the bar. Stalker's wife and child arrive. A mysterious black dog that followed the three men through the Zone is now in the bar with them. His wife asks where he got it; Stalker says that it got attached to him and he couldn't leave it in the Zone. As the Stalker leaves the bar with his family and the dog, we see that his child, nick-named "Monkey" (who earlier dialogue has suggested is affected by some form of genetic mutation as a "child of the Zone") is crippled, and cannot walk unaided. Later, when the Stalker's wife mentions she would like to visit the room, he seems to have doubts about the Zone because he tells her he fears her dreams won't be fulfilled. The film ends with Monkey alone in the kitchen. She recites a poem (written by Fyodor Tyutchev), and then lays her head on the table and appears to telekinetically push three drinking glasses across the table, one after the other, with the last one falling to the floor. As the third glass begins to move, a train passes by (as in the beginning of the film), causing the entire apartment to shake, leaving the audience to wonder whether it was Monkey or the vibrations from the train that moved the glasses.