The Homesmanopens in the 1850s, when early pioneers are doing anything they can to survive dreadful conditions. Women especially struggle with broken hearts and minds as they face bitter hardships: One nineteen-year-old mother loses her three children to diphtheria in three days; another woman left alone for two nights is forced to shoot wolves to protect herself.

The situation calls for a "homesman"-a person charged with taking these women, driven mad by the conditions of rural life, to asylums in the East. Not exactly a job people are lining up for, it falls to Mary Bee Cuddy, an ex-teacher and spinster, who is indomitable, resourceful, and "plain as an old tin pail." Brave as she is, Mary Bee knows she can't make it alone, so she takes along her only available companion: the lowlife and untrustworthy George Briggs.

Mary Bee and George know it won't be easy, but their endurance is truly tested as they fight the tide of colonization, Indian attacks, ice storms, loneliness, and the unceasing aggravation of a disparate group of mad women. This is the tale of their journey and a tribute to the men and women who homesteaded the frontier, whether they survived or not.