Look at the Harlequins! is a fictional autobiography narrated by Vadim Vadimovich N. (VV), a Russian-American writer with uncanny biographical likenesses to the novel's author, Vladimir (Vladimirovich) Nabokov. VV is born in pre-revolutionary St. Petersburg and raised by his aunt, who advises him to "look at the harlequins" "Play! Invent the world! Invent reality!". After the revolution, VV moves to Western Europe. Count Nikifor Nikodimovich Starov becomes his patron (is he VV's father?). VV meets Iris Black who becomes his first wife. After her death—she is killed by a Russian émigré—he marries Annette (Anna Ivanovna Blagovo), his long-necked typist. They have a daughter, Isabel, and emigrate to the United States. The marriage fails; and, after Annette's death, VV takes care of the pubescent Isabel, now known as Bel. They travel from motel to motel. To counter ugly rumors, VV marries Louise Adamson while Bel elopes with an American to Soviet Russia. After the third marriage fails, VV marries again, a Bel lookalike (same birthdate, too), referred to as "you", his final love.

VV is an unreliable narrator who gives conflicting information (e.g., on the death of his father) and seems to suffer from some psychological affliction. When making a full turn while walking—mentally, that is—and tracing his steps back, he is unable to execute the reversion of the surrounding vista in his imagination. He also has the notion that he is a double of another Nabokovian persona.