The main story is a love affair between Alaric Darconville, an English professor at a Virginia women's college, and one of his students, Isabel. The style relies on complex syntax and unusual words. The satire is broad, and uses southern culture cliches but is often very funny. Some of the names of the girls at the school, for example, are Mimsy Borogoves, Barbara Celarent, and Pengwynn Custiss. The story is said to be based on Theroux's years of teaching at Longwood University, and places described in the book are easily recognized buildings on the campus. Patrick O'Donnell calls it a "largely ignored masterpiece". The novel was included by Anthony Burgess in Ninety-Nine Novels: The Best in English Since 1939. It was also nominated for a National Book Award and made the Good Reads list of the 100 Top Literary Novels of All Time. In his review, Stuart Mitchner also indicates that the book is very difficult to read. James Wolcott, writing in the New York Review of Books echoes this sentiment: "To fidgety readers, the 700-plus pages of Darconville’s Cat may seem as long as the Trojan War", but he also calls the book "sly and resourceful."

