The first major theme of the epic narrative is the corruption and disintegration of a family's social fabric due to greed. Two powerful and wealthy ranch owners—who stem from a singular family—violently fight over territories for their respective estates. The violence culminates when the owner kills his own son and then commits suicide by starvation out of guilt afterwards. Doña Luzardo, one of the heirs to the estate, escapes to the more cosmopolitan Caracas to raise her remaining son.

The theme of civilization versus rural savagery is introduced in this section of the book. Doña Luzardo believes that the countryside where the ranch estates are located represents the savage wilderness, in which tribalism among greedy landowners causes massive bloodshed and immorality. On the other hand, the big city represents modern civilization, where there is order and sophistication.

The other major theme—which is evident from the beginning of the novel—is greed that derives from capitalism. The bloody conflicts throughout the novel, especially in the early sections of the book, are all rooted in self-interest and obsession with increasing their respective clan's wealth and power.

The other prominent theme in the novel is the ethnographic study of the plains people of Venezuela, particularly during the early twentieth century. The novel features examples of local dialects, vernacular, and regional culture. The book also examines the socio-psychological profile of the Venezuelan people depicted in the story. This anthropological approach adds context and extra dimensions to the overall narrative, making the central conflict more intense. The microscopic view of a particular locale or culture also serves as the foundation for the story, since the conflict itself is unique to the ranch life of the Venezuelan plains people.

Another major theme is redemption. The titular character who stole the land from the protagonist, Santos Luzardo, gives him the real estate documents that return his family's land to him. Doña Bárbara does this out of her love for Santos. Her act is not only a way for her to wash away her sins of the past, or exclusively as an act of love toward him, but also a way to prevent further bloodshed by unifying the ranch once more. In this sense, she is both the antagonist and true heroine of the story.