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.