The major themes and social concerns throughout Yerby's writing, from the early short stories to McKenzie's Hundred, deal with issues of romance and the warfare of the sexes, the Civil War and Reconstruction, racism, inferiority, slavery, religion (evil, man's relationship with God, man against himself), poor whites, and the decaying Southern aristocracy. Other themes include life in ancient Greece, free will versus fate, societal alienation, illegitimacy, and the problems of human beings irrespective of race, color or religion.

Racism and slave trade are recurring themes. Since The Foxes of Harrow is set in the era of the Civil War, Yerby mentions especially the massacre of Negroes at Fort Pillow, while further debunking the image of the fearless, heroic, Confederate fighter. However, it is the novel Floodtide that devoted itself to a full examination of this theme.

While in The Vixens, Yerby refers to the racist activities...