The narrative begins with the protagonist's attempt to chronicle his own life, only to be perpetually derailed by the complexities of his own birth and family history. Tristram Shandy serves as the narrator of his own biography, yet he finds himself unable to reach the moment of his birth until the third volume, as he is constantly distracted by the eccentricities of his father, Walter, and his Uncle Toby. The world is defined by the limitations of human communication, the fallibility of memory, and the chaotic nature of subjective experience. The narrative framework is highly non-linear, utilizing digressions, blank pages, marbled inserts, and erratic typography to mirror the erratic flow of human thought.

Readers and critics frequently highlight the work as a precursor to modern experimental fiction due to its refusal to adhere to traditional narrative arcs. Discussion often centers on the balance between the comedic character studies of Uncle Toby and the dense, often opaque philosophical digressions that define the narrator's voice. The atmosphere is noted for its playfulness and intellectual irony, which challenges the reader to actively participate in the construction of the story. Many observers point to the text's unique formatting as a deliberate attempt to expose the limitations of the printed word in capturing the complexity of human consciousness.