As the story begins, Charlie is a mildly mentally impaired adult working as a janitor in a factory. He realizes that he is "dumb" and attends night school classes to try to learn to read and write. His motivation and positive attitude so impress his teacher, Miss Kinnian, that she recommends him for an experimental surgery that will triple his current IQ of 68.
Although the procedure is initially a success, the decline of his rodent counterpart Algernon convinces Charlie that his own intelligence is waning. Racing against time, he devotes all his superior intellect to trying to find a way to avoid the decline. What he discovers instead is the Algernon-Gordon effect, a theorem that essentially seals his fate. Realizing his descent into subnormal intelligence (and possibly death) is inevitable, Charlie becomes in turn angry, depressed, and finally, destitute. Out of options, he returns to his job at the factory, where his "friends" Joe and Frank prove themselves true friends by defending him from the teasing of other employees.