Kilgore Trout serves again as the main character, who the author declares as having died in 2001, at the fictitious Xanadu retreat in Rhode Island.

The plot, while centered on Trout, is also a sort of ramble in which Vonnegut relays tangents to the plot and comes back dozens of pages later: the timequake has thrust citizens of the year 2001 back in time to 1991 to repeat every action they undertook during that time.

Kilgore Trout is the only one not affected by the apathy, and thus helps revive others by telling them, "You were sick, but now you're well, and there's work to do."

In the conclusion of this book, a fictionalized Vonnegut (who has inserted himself into the text, something he also did in Breakfast of Champions and, to a lesser degree, in Slaughterhouse-Five) meets other authors for a celebration of Trout.

Though his tone is largely cynical throughout Timequake, Vonnegut frequently makes use of various light-hearted sayings, such as "Hold on to your hats!"