Charlie Jordan words at a bakery in New York City. But there is something a little different about Charlie–he is mentally retarded. He also attends evening classes at Beckman College. Here he submits his progress reports to the research team at the college. In these reports the reader is revealed Charlies experiences in the bakery where the owner has brought him from the Warren State Home, an institute for mentally retarded.
He soon becomes a part of the bakery, and considers his co-workers as friends. From these reports, the team has considered Charlie a prime candidate for an experimental surgery, which if effective, would improve his intelligence. Soon begins Charlies preliminary testing. For weeks and weeks on end, Charlie undergoes simple tests of ordinary tasks, and competes in racing with a mouse.
He becomes depressed when the mouse beats him every time. The operations takes place soon after, and Charlie becomes more disappointed with immediate results. However, he is assured that he will progress gradually, and steadily. Over a short period of time, he begins to read more, win more mazes, and master some complex processes at the bakery.
His co-workers begin to resent him, and he is completely disillusioned. He now has to spend more and more time being tested at the lab. Charlie learns that the mouse Algernon, whom he constantly competes with, has also undergone a surgery similar to his own, and accounts for his intelligence. Charlie surges ahead in knowledge, and masters languages. He begins to see his supportive teacher from the college, Alice, as an attractive young woman.
They become extremely close, and Charlie eventually tries to make love to her. On these several occasions, he finds that he suffers a violent physical reaction while trying and has to stop. He cannot understand why this is happening to him. At this same time, Charlie begins re-living repressed memories of his childhood, and is disturbed by images of his mother pushing him to study, or his being neglected in favor of his sister. He is upset, and even frightened, but he finds his newfound intellectual ability more thrilling and keeps working hard.
The scientists at the lab report to Charlie that he and Algernon are to be taken to Chicago for a convention, in which the head scientist will present the findings of his team. Once they arrive, Charlie and Algernon are the prime exhibits and Charlie is humiliated by some remarks made. He also discovers that the researchers had not given sufficient time to verify their results of Algernon before performing the experiment on Charlie. Charlie and Algernon run away to New York, and Charlie decides his time is probably short, and begins to try and trace the reasons for his experiments failure. Alice and Charlie cannot overcome their problems, and she is forced to move on.
He soon gets involved with Fay, his neighbor and unconventional artist. Around her, he is able to defeat his inhibitions. But as Charlies work becomes harder and more time constraining, they too break up. Algernon the mouses condition worsens as a whole, and he finally dies.
Charlie sees this as a sigh of doom, and knows that his own time is approaching. He seeks his parents out, and meets his father, but cannot bear to introduce himself. He then meets his sister and his mother, and brags about his accomplishments, makes peace, and continues on. Charlie meets the scientist Nemur at a party, and sites him as being insensitive. Nemur charges Charlie as selfish and arrogant, which Charlie does readily accept. Charlie also comes to terms with his old Charlie, and accepts himself as an important and enduring part of him.
Charlie and Alice get together once more, but only to find their own fulfillment for a short time. As his mind