The life of a San Francisco dentist unravels when his marriage to a woman who wins a lottery prize triggers a descent into greed, violence, and moral decay. McTeague, a man of limited intellect and immense physical strength, operates an unlicensed dental practice on Polk Street until his marriage to Trina Sieppe introduces the corrupting influence of sudden wealth. As Trina becomes obsessed with hoarding her lottery winnings, McTeague loses his livelihood and his sense of self, leading to a volatile domestic environment. The narrative follows a third-person objective perspective, documenting the characters' slow degradation under the pressures of poverty and avarice. The world is defined by the harsh, deterministic constraints of urban San Francisco, where biological impulses and economic forces dictate the characters' fates.

Readers and critics frequently identify this work as a foundational example of American naturalism, noting its unflinching focus on the darker aspects of human nature. Discussion often centers on the author's clinical, almost detached observation of the characters' inevitable decline as they are crushed by forces beyond their control. Many highlight the effectiveness of the setting, which functions as a character in its own right, mirroring the internal decay of the protagonists. The balance between the slow, methodical pacing of the early chapters and the violent, desperate conclusion is a common point of analysis for those examining the author's stylistic choices.