The novel's main protagonist, from whose point of view nearly the entire story is told. Intelligent and vivacious, Carol Milford attends college in Minneapolis and then works as a librarian in St. Paul for three years before marrying Dr. Will Kennicott and moving to Gopher Prairie. An incurable romantic, she yearns to bring beauty and culture to the ugly towns of the Middle West. Her failed attempts to reform Gopher Prairie provide the novel's main conflict. Unhappy with her life in Gopher Prairie, Carol seeks escape through books and a romantic friendship with a young man named Erik. In the end, however, the town defeats her. She leaves Gopher Prairie to move to Washington, D.C., but returns and accepts the town as it is. Throughout the novel, her marriage to Kennicott endures its ups and downs, although she continues to love and admire him. Lewis loosely based Gopher Prairie on his own hometown of Sauk Centre, Minnesota, and the character of Carol on himself.
The novel's secondary protagonist. Dr. Will Kennicott provides a foil to his wife, Carol. While she also desires achieving social change and individual happiness, he feels satisfied with his life and prefers to maintain the status quo. While Carol is romantic and interested in the fine arts, Kennicott is realistic and materialistic, interested only in making money and taking care of his family and patients. Will sets Carol on a pedestal and admires her, regardless of her whims. As they drift apart, however, he begins a short-lived secretive affair with Maud Dyer. When Carol moves to Washington, Kennicott visits her and courts her a second time in order to persuade her to return to Gopher Prairie.
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Gopher Prairie's high school teacher. Vida becomes one of Carol's best friends, often serving as a buffer between Carol and Gopher Prairie, as she understands both points of views. Because she once loved Will Kennicott herself, Vida develops a love-hate relationship with Carol and tries to become her adviser. While the two women share many interests, they gradually drift apart when Vida marries Raymond Wutherspoon and devotes herself to housework.
Another important friend of Carol's. Guy is an intelligent, middle-aged bachelor lawyer. Although Carol admires him briefly, she discovers, to her disappointment, that he maintains a defeatist attitude and feels quite content doing nothing important with his life. During an important conversation with Carol, Guy explains that he suffers from the "Village Virus," a disease that saps the will of ambitious people who live in small towns.
A warm and friendly woman who becomes Carol's maid and good friend. Bea also acts as another foil to Carol. Arriving in Gopher Prairie on the same day as Carol, Bea makes a very different assessment of Gopher Prairie, finding the town beautiful and exciting. Bea marries Miles Bjornstam and tragically dies.
Gopher Prairie's town handyman. Miles, who supports socialism and the Democratic Party, is largely scorned by the citizens of Gopher Prairie, who consider him slightly insane. Carol, however, finds him to be a kindred spirit because she shares many of his liberal views. Although Bjornstam settles down after his marriage to Bea, he leaves Gopher Prairie forever when his wife and son, Olaf, die.
A young tailor in his twenties who finds himself ridiculed by the townspeople because of his attractive feminine appearance and interest in books. Erik embarks on a romantic friendship with Carol, much to her delight, but leaves Gopher Prairie to avoid creating a scandal.
The new high school teacher in town. Fern, who is physically active and intelligent, becomes Carol's friend. She leaves town, however, when a student, Cy Bogart, falsely accuses her of corrupting him. Fern's tragedy provides Lewis with way to demonstrate and ridicule the hypocrisy of Gopher Prairie.
A wealthy automobile manufacturer originally from Gopher Prairie who allegedly has attained nationwide fame. Bresnahan is much admired by the people of the town, who admire material success. Carol, however, finds him coarse and overbearing. She admires Bresnahan for his importance, but discovers in Washington that in reality he is relatively unimportant.
A rather spineless man who marries Vida Sherwin. Raymond becomes more courageous and upstanding, however, due to his wife's prodding. He enlists in World War I and comes back to Gopher Prairie a hero.
Carol and Kennicott's infant son. Hugh, who is named after Carol's deceased father, is very much like his own unimaginative father, Will.
Carol's nosy neighbor and the town's gossip. Mrs. Bogart is very much a religious hypocrite, creating a scandal out of nothing when her boarder, Fern Mullins, innocently attends a barn dance with her son, Cy Bogart, the town's juvenile delinquent.
Kennicott's relatives who move to Gopher Prairie and prove to be a constant source of annoyance to Carol. Aunt Bessie joins her friend, Mrs. Bogart, as one of the town's biggest gossips.
The wife of to Dave Dyer, the town druggist. Maud is a neurotic hypochondriac with whom Kennicott begins a secretive affair as his relationship with Carol deteriorates.