Charlie Gordon is a mentally disabled young man who is a part-time baker. Alice, the teacher at the special school that he attends, suggests him to undergo an operation to increase his intelligence. In one pre-treatment tests, Charlie sees how a mouse named Algernon manages to get out of an elaborated maze—something that he has not been able to do.
After surgery, Charlie's intellectual abilities improve dramatically. He realizes that until then many people have made fun of him because of his "differentness". Doctor Strauss, who treats Charlie, asks him to accompany him to a surgery conference. Strauss's speech shocks Charlie, who gives a very harsh speech towards the scientist and prophesies, based on the results obtained with a similar experiment by a Russian researcher, that he could soon return to the previous level; Charlie then causes panic by releasing some mice into the classroom.
Back home, Dr. Strauss confesses that he knows the results of the Russian experiments; as if that was not enough, Algernon starts feeling ill. Charlie decides to use the little time that is left for him to try to find a solution to the problem. He realizes that he was wrong to focus everything on the rational part of him and goes to visit his mother, with whom he had severed all relationships many years ago.
Algernon dies in the hands of Charlie, who secretly buries him to prevent him from being dissected. He goes back to the bakery. Saying goodbye to Alice, who is in love with him, heartbroken at how the situation has evolved, he asks her to bring flowers to Algernon's grave.