The action covered in Tristram Shandy spans the years 1680-1766. Sterne obscures the story's underlying chronology, however, by rearranging the order of the various pieces of his tale. He also subordinates the basic plot framework by weaving together a number of different stories, as well as such disparate materials as essays, sermons, and legal documents. There are, nevertheless, two clearly discernible narrative lines in the book.

The first is the plot sequence that includes Tristram's conception, birth, christening, and accidental circumcision. (This sequence extends somewhat further in Tristram's treatment of his "breeching," the problem of his education, and his first and second tours of France, but these events are handled less extensively and are not as central to the text.) It takes six volumes to cover this chain of events, although comparatively few pages are spent in actually advancing such a simple plot. The story occurs as a series of accidents, all of which seem calculated to confound Walter Shandy's hopes and expectations for his son. The manner of his conception is the first disaster, followed by the flattening of his nose at birth, a misunderstanding in which he is given the wrong name, and an accidental run-in with a falling window-sash. The catastrophes that befall Tristram are actually relatively trivial; only in the context of Walter Shandy's eccentric, pseudo-scientific theories do they become calamities.

The second major plot consists of the fortunes of Tristram's Uncle Toby. Most of the details of this story are concentrated in the final third of the novel, although they are alluded to and developed in piecemeal fashion from the very beginning. Toby receives a wound to the groin while in the army, and it takes him four years to recover. When he is able to move around again, he retires to the country with the idea of constructing a scaled replica of the scene of the battle in which he was injured. He becomes obsessed with re-enacting those battles, as well as with the whole history and theory of fortification and defense. The Peace of Utrecht slows him down in these "hobby-horsical" activities, however, and it is during this lull that he falls under the spell of Widow Wadman. The novel ends with the long-promised account of their unfortunate affair.