Fifty-three year old Russian emigre Timothy Pnin is marked by his inability to fit in to western society as a professor at Waindell College. The plot largely functions as an episodic look at Pnin's many blunders that cause him misfortune. Examples include missing a lecture because he took the wrong train and failing his drivers test.

To make matters worse, his ex-wife, Liza Wind, soon re-appears in his life under the pretense of wanting to reconnect with him. However, the truth is that she plans to leave her current husband for a poet and no longer wants any responsibility for her child, Victor Wind. Oblivious that the child is not his, Pnin agrees to support him. Surprisingly, Victor admires Pnin far more than he ever did his birth parents, and the two share many characteristics.

In the end, to his surprise, Pnin is fired and replaced by the narrator when Dr. Hagen, the only Waindell faculty member that admired him, leaves his position. The novel ends with Pnin driving away. However, the tone is less tragic than it is optimistic, symbolizing the vulnerable and endearing nature of Pnin.

Timofey Pnin, an instructor of Russian at Waindell College, is taking a train to give a lecture to the Cremona Women’s Club. Sadly, he is on the wrong train. The discovery of his mistake and his subsequent attempts to get to Cremona in time for the lecture cause him to undergo a sinking spell: He plunges into a recollection of a time in his childhood when he suffered from a fever and struggled in vain to find the key to the recurring pattern of foliage on his wallpaper. The spell passes, but when he is about to begin his lecture he has a fleeting sense that some of the beloved people from his past, including his parents, are in the audience.

Pnin moves into a room rented to him by Joan and Laurence Clements. The room has been vacated by the Clements’ daughter Isabel, who has married and moved away. Pnin learns that his former wife, Liza Wind, wants to visit him. Pnin’s marriage to Liza ended when she abandoned him for Eric Wind. When Liza arrives, she tells Pnin that she would like him to send some money in her name to her son Victor at boarding school. After her departure, Pnin is devastated with sorrow, and he resists all attempts by Joan Clements to cheer him up.

Pnin continues his routine at Waindell College, teaching classes and conducting research on the history of Russian culture. The librarian indicates to Pnin that Isabel’s marriage is in trouble and that he might have to relocate, but he does not pay full attention to her words. In the evening, Pnin watches a Soviet propaganda film and imagines himself back in the Russia of his youth. As he falls asleep that night, he is awakened by the noisy return of Isabel, who is about to burst into her old room until she is stopped by her mother.

Lisa’s son Victor visits Pnin in Waindell. Victor has a recurring dream in which his father is a king who is forced into exile by a revolution in his country. Victor has an extraordinary IQ and is a talented artist. During his correspondence with Pnin, he begins to develop a fondness for this man who, in Victor’s eyes, has an exotic background. On the night of his arrival, Victor, who usually suffers from insomnia, falls asleep instantly, while Pnin seems to step into Victor’s dream, as he sees himself fleeing from a castle and pacing a deserted shore while awaiting the arrival of a boat to take him to safety.

Pnin visits a summer retreat in the woods of New England, where he finds a collection of Russian émigrés much like himself. Immersed in the culture and companionship of his fellow intelligentsia, Pnin seems fully relaxed. One woman staying at the summer house mentions Mira Belochkin, the woman Pnin had loved in his youth, and this causes Pnin to reflect upon his old romance. However, he is also reminded of Mira’s terrible death in a Nazi concentration camp.

Pnin moves into a house he has rented on his own, and he throws a housewarming party to celebrate the event. One of his guests is his protector at Waindell, Dr. Hagen, who will soon be leaving the college to move to a more prestigious institution. With Hagen’s departure, Pnin will be out of a job, and when Hagen learns that Pnin is thinking of buying his rented house, Hagen informs Pnin of his bleak prospects. Pnin is troubled by the news, and when he washes dishes later that night, he absentmindedly drops a nutcracker into the soapy water, and he hears the sound of breaking glass. He fears that the broken object is a wonderful punch bowl given to him by Victor but learns to his relief that it was only a wine glass. The marvelous bowl is intact.

In the final chapter of the novel, the narrator, who has remained in the background until now, comes to the fore and begins to describe his own memories of Pnin. The narrator had an affair with Liza before she married Pnin (and it was apparently her suicidal despair over the outcome of the affair that led her to accept Pnin’s proposal). The narrator has accepted a job at Waindell College, and he has offered a position to Pnin as well, but Pnin refuses to work under his old acquaintance. As the novel ends, the narrator arrives in Waindell and catches a glimpse of Pnin driving out of town, leaving the narrator behind in his stead.