Though the novel is entitled Odd Woman, the protagonist, Jane Clifford, is far from odd, as her situation as a thirty-two-year-old American woman who is both unmarried and well-educated in the 20th century is not too uncommon (and even more common today). She, like many other women during that time, struggles to find meaning in her life and figure out where she fits. She feels odd because unlike generations before her, she is not married yet and instead is in a dead-end relationship with her lover, Gabriel Weeks, a married professor unwilling to commit to her.

At the start of the novel, Jane is a substitute college professor of British literature in the Midwest facing an uncertain future. When her grandmother dies, she travels back south to her roots where she reflects on her past, explores the lives of the women in her family, and compares their lives—as well as the lives of her colleagues—to her own life.

Through Jane, we meet the other female characters whom she compares herself to. There is Edith Barnstoff, her grandmother, who is classy, dignified, and a traditional Southern woman. Jane also learns of Edith's sister, Cleva Dewar, who followed her heart and ran away with an actor who later abandoned her. Then there is Kitty Barnstoff Clifford Sparks, her mother, who quit her career as a teacher/writer to devote herself to her second husband. There is also a new generation of women. First, there is Gerda Mulvaney, an old college friend, who is single, divorced, and committed to fighting for feminism. There is also Sonia Marks, a new friend and colleague, who seems to have the perfect balance between a career and a successful marriage.

All of these women represent the different roles of women through the generations, and through them the author offers the diversity of women's identities—past and present. The question is, which of these roles best fits Jane? Do any fit or none at all? Perhaps she will find her own role.