The central conflict arises from the divergent paths taken by Jim Burden and Ántonia Shimerda as they transition from their shared childhood on the Nebraska frontier into adulthood. Jim Burden, the narrator, observes the immigrant experience and the harsh realities of pioneer life through his evolving relationship with Ántonia, the daughter of Bohemian settlers. As Jim pursues an academic and professional life in the East, Ántonia remains anchored to the land, facing the physical hardships of farm life and the social pressures of her community. The narrative is framed as a reflective memoir, utilizing Jim's adult perspective to reconstruct his formative years and the landscape that shaped them.

Discussion often centers on Cather's ability to elevate the mundane details of pioneer life into a mythic representation of the American frontier. Readers frequently highlight the lyrical quality of the prose, which balances the harshness of the environment with a deep affection for the characters. Critics often examine the gender dynamics and the way Jim's idealized memory of Ántonia serves as a lens for his own search for identity. The novel is widely recognized for its atmospheric world-building and its focus on the internal development of its protagonists over the course of several decades. Many readers appreciate the understated emotional resonance that persists throughout the narrative.