Tristram is the titular narrator attempting to write a comprehensive autobiography. His effort to document his life constantly diverts into extensive anecdotes about his family members and their peculiar obsessions. He suffers several early physical and social misfortunes, including a crushed nose and a heavily disliked christened name, which deeply shape his self-perception. Despite these setbacks and his declining physical health, he maintains a wry sense of humor and a tolerant outlook toward others.

Walter is a retired businessman who spends his time at the Shandy country estate pursuing esoteric intellectual obsessions. He reads classical texts voraciously and applies obscure theories to everyday life, particularly believing that names and nose sizes dictate a person's fate. He prioritizes abstract debates over practical action, famously spending years writing a manual on child-rearing rather than actually raising his son.

Toby is Walter's brother and a retired army captain who suffered a severe groin injury during the Siege of Namur. He copes with the lingering trauma of his military service by building an elaborate, scale-model replica of the battlefield in his garden. He possesses a remarkably gentle disposition, famously refusing to harm a fly, and he treats everyone with profound compassion.

Yorick is the local parson and a close associate of the Shandy family. He maintains a highly jovial attitude and an active wit, contrasting with the typical solemnity expected of his profession. He rides an unkempt horse to avoid accusations of pride and frequently amuses himself by listening to Walter and Toby's eccentric conversations.

Elizabeth is Walter's wife and Tristram's mother. She contrasts sharply with her husband's argumentative nature, preferring to remain passive and agreeable to avoid escalating his frequent rants. She exercises her legal marriage rights to demand a local female midwife for her labor rather than relying solely on the male doctor Walter prefers.

Dr. Slop is a Catholic country physician who prides himself on his scientific knowledge of obstetrics. He views traditional midwives with disdain and prefers relying on his newly invented medical instruments. His attempt to assist in Tristram's delivery using his custom forceps results in permanent damage to the baby's face.

Corporal Trim is Toby's loyal servant and former military subordinate. He actively encourages and assists in the construction of the miniature battlefield, viewing the world through the same military framework as his master. He is highly devoted to the Shandy family but occasionally interrupts tasks to share lengthy stories of his own past.

Widow Wadman is a neighbor of the Shandy family who develops a strong romantic attachment to Uncle Toby. She strategically maneuvers herself into his life by feigning interest in his model fortifications. She harbors intense anxiety regarding the exact nature and location of his battle wound, fearing it may impact their potential physical relationship.

Susannah is a chambermaid in the Shandy household. She acts as a messenger during chaotic moments, such as relaying news of Tristram's declining health during delivery. Her poor memory directly results in Tristram receiving the wrong name during his rushed baptism.

Obadiah is a manservant at the Shandy estate. His attempts to carry out orders quickly often result in physical comedy or disaster, such as knocking the doctor off his horse or tying medical bags with impossibly tight knots to silence their rattling.

The unnamed midwife is a practical, community-focused woman who delivers babies in the local village. She operates with traditional methods and fiercely defends her jurisdiction when forced to work alongside the technically-minded Dr. Slop.

Bridget serves in Widow Wadman's house and becomes a crucial intermediary in the romantic maneuverings between the two households. She receives direct orders from her employer to quietly investigate the physical capabilities of Toby.

Bobby is Walter and Elizabeth's eldest son, who spends his time away at school. His sudden passing profoundly shifts the family dynamic, altering Walter's financial plans and making young Tristram the central focus of the Shandy legacy.

Lieutenant Le Fever is an impoverished, sick soldier encountered by Toby and Trim. He represents the camaraderie of army life, bonding with his fellow veterans in his final days before passing his legacy onto them.

Billy is the orphaned son of Lieutenant Le Fever. After attempting a military career that ends in ill health and financial ruin, he is taken in by Toby, who views him as an adopted son and candidate to help educate Tristram.