The novel begins with the introduction of Timofey Pavlovich Pnin, a professor of Russian at Waindell College, who is "ideally bald" with a "strong man torso," short "spindly legs," and "feminine feet." Pnin is on a train en route from Waindell to Cremona, where he is to give a guest lecture. Pnin is persistently bothered by the fear that he may lose his lecture papers, or muddle them with the student essay he is correcting. He discovers he has boarded the wrong train and gets off. When he tries to board a bus to Cremona, he suddenly realizes he has lost his luggage (with his papers) and has a fit of dizziness. He arrives at Cremona, and is about to give his lecture when he experiences a vision, seeing his dead parents and friends from before the Russian Revolution in the audience. The chapter ends without revealing whether Pnin has the correct papers.
Laurence Clements, a fellow Waindell faculty member, and his wife Joan, are looking for a new lodger after their daughter Isabel has married and moved out. Their new tenant happens to be Pnin himself, who has been informed of the vacancy by Waindell's librarian, Mrs. Thayer. Although at first skeptical of lodging a man with such an unfavorable reputation (Laurence refers to him as a "freak"), the Clementses grow to enjoy Pnin's eccentricities and his idiosyncratic phrasings. There follows the history of Pnin's relationship with his ex-wife Dr. Liza Wind, who manipulated him so that she might come to America and marry another man, fellow psychologist Eric Wind. Liza visits Pnin, but only wants to extract money from him for her son, Victor. Although Pnin is aware of her schemes, he obliges out of his still-present love for his ex-wife. After Liza leaves, Pnin breaks down from her cruelty, shouting "I haf nofing left, nofing, nofing!"
Pnin is alone at the Clementses' as they have gone west to visit Isabel. Descriptions are then given of Pnin's competency in Russian, and this is sharply contrasted with his bumbling English. He arrives at Waindell library, where he ignores Mrs. Thayer's attempts at small talk as he tries to return a book requested by another patron. When the record shows the requester to be Pnin himself, he leaves to do research for his book, a " Petite Histoire of Russian culture." The chapter ends with the return of Isabel, newly divorced, so that Pnin is forced to find new a new home.
The fourth chapter opens with the dream of fourteen-year-old Victor Wind, who envisions a King of a foreign land who refuses to abdicate and is exiled (foreshadowing the still unwritten Pale Fire ). Victor considers this King to be his real father, rather than his biological father Eric Wind, whom he has not seen for two years. Victor is depicted as an ingelligent, nonconformist boy with a great talent for drawing. His parents, incapable of understanding him, have him psychoanalyzed. him as if Victor's artistic ability were detrimental, much to the boy's chagrin. Victor has little respect for his teachers at St. Bart's except for Lake the art teacher, "a tremendously obese man with shaggy eyebrows and hairy hands." Victor is to meet with Pnin at Waindell bus station, and Pnin hurriedly buys him a soccer ball and the Jack London novel The Son of the Wolf . Pnin meets Victor and is immediately surprised by the boy's physical and mental maturity. But Victor is not interested in soccer, and Pnin takes the entire encounter as a failure, unaware that Victor holds him in great admiration.
Pnin, newly licensed, is driving to The Pines, the summer home of anémigré friend, where he meets an assembly of Russian intellectuals, and in this company, Pnin, normally awkward and out of place in English-speaking society, transforms into a distinguished gentleman with an encyclopedic knowledge of Russian culture who excels at croquet. The conflict between these Russian émigrés and their American-raised children is shown at The Pines, where the younger generation scoffs at the alien interests of their parents. A mutual friend mentions Pnin's former sweetheart, the Jewish Mira Belochkin, who was murdered at Buchenwald, the Nazi concentration camp. Another refers to Vladimir Vladimirovich, an expert on butterflies, who is later revealed to be the narrator of Pnin.
Pnin has finally decided to rent a house of his own. To celebrate this momentous event, he invites the Clementses, Mrs. Thayer, several Waindell faculty members, and his former student Betty Bliss to a "house-heating party." Although the party is somewhat successful, Pnin is informed by Dr. Hagen, the chair of his department, that a new department of Russian is to be formed, under whom Pnin categorically refuses to work. Pnin almost breaks a magnificent glass punch bowl, a gift of Victor and a symbol of his regard.
Finally the identity of the narrator is revealed—a Russian-American academic and lepidopterist called Vladimir Vladimirovich. V.V. recounts his version of his meetings with Pnin, claiming that they first meet when V.V. had an appointment with Pnin's father, Pavel, an ophthalmologist. V.V. had an affair with Pnin's ex-wife Liza just before Pnin's marriage and nearly drove her to suicide by insulting her mediocre "Akhmatovasque" poetry. V.V. patronises Pnin, and many of his claims conflict with events V.V. himself narrated earlier in the book. V.V. is revealed to be the new head of the Waindell Russian department and invites Pnin to stay, but Pnin leaves Waindell, taking a stray dog with him. The novel closes with Jack Cockerell, head of English at Waindell, beginning to tell V.V. the story of Pnin bringing the wrong lecture papers to Cremona, bringing the narrative full circle.