Carol Milford attends Blodgett College in Minneapolis and dreams about settling down in a prairie village and transforming it into a place of beauty. After graduation, she works as a librarian at St. Paul for three years. She meets Dr. Will Kennicott at a friend's house, and he begins courting her. After courting for a year, they marry and move to Kennicott's hometown of Gopher Prairie. Disappointed by her first impression of the Gopher Prairie, Carol finds the town to be ugly and the townspeople to be provincial. The townspeople gossip all the time and are completely uninterested in cultural or social issues. Mrs. Bogart, the Kennicotts' neighbor, proves to be a religious hypocrite who idly gossips about everyone. However, Bea Sorenson arrives in Gopher Prairie on the same day as Carol. Awestruck by the magnificence of the town, which is larger than any she town has ever seen, Bea decides to stay and becomes Carol's maid.

Carol refurbishes Kennicott's old-fashioned house with modern furniture and makes elaborate preparations for a party, a party unlike any party the town has ever seen. However, Carol discovers that the dull townspeople do not like change. Furthermore, she feels disheartened to learn that the townspeople constantly watch her every move and criticize her for being different from them. They criticize the way she dresses and the way she acts. She finds few friends in Gopher Prairie, except for the lawyer, Guy Pollock, and the high school teacher, Vida Sherwin. Carol also becomes friends with her maid, Bea, and the town's handyman, Miles Bjornstam. While the townspeople treat Miles as an outcast because he supports socialism and the Democratic Party, Carol finds herself drawn to him.

Carol tries to get the people to build a new city hall, school, and library, and a more comfortable rest room for the farmer's wives. However, no one shares her interest in constructing new buildings or helping the town's poor. Everyone tells her that they do not want to spend money on unnecessary things like buildings. Carol idealizes Guy Pollock, thinking that he shares her interest in reforming the town. However, she eventually finds out that he does not care for social reform and that he has settled down to enjoy small town life. As Guy explains to Carol, he has the "Village Virus."

Carol joins the Jolly Seventeen, the women's social club, and the Thanatopsis Club, the women's study group. When she tries to change the unimaginative club programs, the other members ignore her suggestions. Along with a group of friends, Carol forms a drama group and stages a play, which turns out to be horribly mediocre. Appointed to the library board, she eagerly makes suggestions to how the library could encourage reading, but the local librarian opposes her suggestions, preferring to discourage readers in order to keep the books clean.

Carol and Kennicott have a bitter argument in which he accuses her of feeling superior to everyone else in town. After they make up, she begins to fall in love with him all over again. She idealizes him as a heroic doctor and witnesses him amputating a farmer's arm one night. But life in Gopher Prairie continues to offer Carol no challenges. She gives birth to a boy, whom she names Hugh after her deceased father. Kennicott's aunt and uncle, the Smails, come to live in Gopher Prairie and prove a constant irritation to Carol.

Meanwhile, Bea and Miles Bjornstam marry. The townspeople still shun Bjornstam and do not visit his household. Unfortunately, Bea and her son Olaf die from typhoid. Heartbroken, Bjornstam leaves town, and the townspeople blame him for his family's deaths. Then, Carol's friend Vida Sherwin marries Raymond Wutherspoon, another local. When World War I breaks out, Raymond joins the army. Although Kennicott also wants to enlist, the medical council requests that he stay in Gopher Prairie to provide his services.

Erik Valborg, the son of a Swedish farmer, comes to Gopher Prairie to work as the tailor's assistant. Fern Mullins, a young teacher, also arrives in Gopher Prairie and boards in Mrs. Bogart's house. Carol finds the company of these two new residents stimulating because they share her love for books, music, dance, and drama. Cy Bogart, the leader of the town's gang of boys and Mrs. Bogart's son, ruins Fern's reputation when he falsely accuses Fern of getting him drunk and making sexual advances on him. Forced to resign from the school, Fern leaves Gopher Prairie.

Erik finds himself attracted to Carol and goes out with her for long walks. Kennicott knows about the close relationship between Erik and Carol but does not really mind because he knows that the two are only good friends who share the same intellectual interests. As Carol and Kennicott's marriage deteriorates, he begins an affair with Maud Dryer. However, after Fern leaves town, Kennicott decides that Carol and Erik should stop seeing each other in order to avoid another scandal. Erik leaves Gopher Prairie.

Kennicott then decides to take Carol on a long tour of California in order to get away from the gossips in Gopher Prairie. When they return, Carol feels tired because the hypocrisy and narrow-mindedness of the people of Gopher Prairie has not changed at all. She decides to leave and takes her son, Hugh, with her. Although Kennicott feels distressed when Carol leaves, she assures him that she will return someday. Carol moves to Washington, D.C., where she works for two years. Though she enjoys the beautiful city, she feels lonely in its largely anonymous crowds. Kennicott visits Carol in Washington and begins courting her for the second time. Recognizing her husband's love, Carol decides to return to Gopher Prairie.

Carol's experience in Washington helps her acquire maturity and a new outlook toward life. She determines that she can at least play a small role in changing life in Gopher Prairie. When Carol returns, she accepts the small town and its people as they are. However, she still fights small battles to make the town a better place. She gives birth to a daughter, hoping that the child will continue her fight. In the closing lines of the novel, while Carol talks about her struggle reform Gopher Prairie, Kennicott only half-listens to her and thinks only about the weather.