As its title suggests, the book is ostensibly Tristram's narration of his life story. But it is one of the central jokes of the novel that he cannot explain anything simply, that he must make explanatory diversions to add context and colour to his tale, to the extent that Tristram's own birth is not even reached until Volume III.
Consequently, apart from Tristram as narrator, the most familiar and important characters in the book are his father Walter, his mother, his Uncle Toby, Toby's servant Trim, and a supporting cast of popular minor characters, including the chambermaid, Susannah, Doctor Slop, and the parson, Yorick.
Most of the action is concerned with domestic upsets or misunderstandings, which find humour in the opposing temperaments of Walter—splenetic, rational, and somewhat sarcastic—and Uncle Toby, who is gentle, uncomplicated, and a lover of his fellow man.
In between such events, Tristram as narrator finds himself discoursing at length on sexual practices, insults, the influence of one's name, and noses, as well as explorations of obstetrics, siege warfare, and philosophy as he struggles to marshal his material and finish the story of his life.
Though Tristram is always present as narrator and commentator, the book contains little of his life, only the story of a trip through France and accounts of the four comical mishaps which shaped the course of his life from an early age. Firstly, while still only a homunculus, Tristram's implantation within his mother's womb was disturbed. At the very moment of procreation, his mother asked his father if he had remembered to wind the clock. The distraction and annoyance led to the disruption of the proper balance of humours necessary to conceive a well-favoured child. Secondly, one of his father's pet theories was that a large and attractive nose was important to a man making his way in life. In a difficult birth, Tristram's nose was crushed by Dr. Slop's forceps. Thirdly, another of his father's theories was that a person's name exerted enormous influence over that person's nature and fortunes, with the worst possible name being Tristram. In view of the previous accidents, Tristram's father decreed that the boy would receive an especially auspicious name, Trismegistus. Susannah mangled the name in conveying it to the curate, and the child was christened Tristram. According to his father's theory, his name, being a portmanteau-like conflation of "Trismegistus" (after the esoteric mystic Hermes Trismegistus) and "Tristan" (whose connotation bore the influence through folk etymology of Latin tristis, "sorrowful"), both doomed him to a life of woe and cursed him with the inability to comprehend the causes of his misfortune. Finally, as a toddler, Tristram suffered an accidental circumcision when Susannah let a window sash fall as he urinated out of the window because his chamberpot was missing.