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Arrowsmith tells the story of bright and scientifically minded Martin Arrowsmith of Elk Mills, Winnemac (the same fictional state in which several of Lewis's other novels are set), as he makes his way from a small town in the Midwest to the upper echelons of the scientific community at a prestigious foundation in New York City. Along the way he begins medical school. He becomes engaged to one woman, cheats on her with another woman, becomes engaged to the second woman and then finally invites both women to a lunch to settle the issue. He eventually insults his mentor, Max Gottlieb, and is suspended from school. He takes up life as an ordinary worker, then marries Leora with her family supporting him based on the promise that he will take up private practice as the only doctor in tiny Wheatsylvania, North Dakota. Frustrated with the work, he moves on to a job at the state Department of Public Health branch in Nautilus, Iowa, then becomes romantically involved with the young daughter of its local director. After a series of political disputes, he resigns and joins the staff of an exclusive private hospital in Chicago. Finally, Arrowsmith is recognized by his former mentor, Gottlieb, for a scientific paper he has written, and is invited to take a post with a wealthy and elite research institute in New York City. The book's climax deals with Arrowsmith's discovery of a phage that destroys bacteria and his experiences as he faces an outbreak of bubonic plague on a fictional Caribbean island.