In a dreamlike prologue, Jo and the company sing a hymn ("Hand in the River").
Decades earlier, in Boston, 1871: after giving birth to a child out of wedlock, nineteen-year-old Josephine Monaghan heads west on her own to find a way to support herself and her infant son. On the train, she encounters a group of fellow travelers who are searching for their piece of the American dream by joining the silver rush ("Train to San Francisco"). Put off the train in rural Idaho by a disgruntled conductor, Josephine is initially helped by a kindly tinker and is optimistic ("Life"). That night, she is kidnapped and violently attacked by two itinerant soldiers. In desperation, she discards all traces of femininity as a way of protecting herself in the harsh landscape, donning men’s clothing and deliberately disfiguring her face ("Everything That Touched Her").
Passing herself off as a man, Jo makes her way to the rough mining town of Silver City ("Far From Home"). She befriends a young couple, Sara Stewart and Jordan Ellis. Sara takes pity on Jo and sells her an unused plot of land, coercing Jordan into helping Jo learn how to mine silver ("Muscle and Sweat"). Jordan wants to marry Sara, but she demurs ("Whatcha Gonna Do?"). Jordan, Jo, and the miners work the harsh soil and eventually make a strike ("Hi-Lo-Hi"). Sara struggles with her newfound feelings for Jo, who in turn is deeply attracted to Jordan ("There Is This Man"). Jordan comes to regard Jo as his best (male) friend. The town prepares for the coming storm and the cessation of work ("To Winter"). After a large mining company moves into the area, Jo sells her claim and uses the money she has acquired to return East for her son. Sara and Jordan are sorry to see her go ("After You"). Discovering that her family in Boston has adopted her son ("Everything That Touched Her" Reprise) Jo returns to Silver City and her male identity, just as Jordan and Sara are being married ("A New Beginning").
Eighteen years later, the rough mining camps have given way to a civilized town, and its citizens celebrate Idaho’s statehood ("Independence!"). Jo has opened a General Store with Jordan, never revealing her longing for him. Sara still harbors feelings for Jo and grows increasingly distant from Jordan. Living alone in a remote cabin, Jo has become a prisoner of bitterness. Unrest has begun to grip the town as less and less silver is being mined. They fear that the mining company will hire Chinese laborers who work for half-pay, and then eventually shut the mines down. A Chinese man, Tin Man Wong, appears at the edge of the crowd and is attacked. Jordan and Sara protect the stranger by taking him to recover at Jo's cabin, over her objections. At the same time, Jo learns that her adult son, Lawrence, has discovered her existence and is heading for Idaho to find her ("Life" Reprise). The presence of Tin Man, who continues to recover, and the letters from her son begin to reveal a vulnerability Jo has long hidden from view. Jordan attempts to rekindle his marriage to Sara ("When You Love Someone"), but she remains conflicted ("Troubled Heart").
When the mine shuts down, the town turns Tin Man into a scapegoat ("Hi-Lo-Hi" Reprise). He tells Jo that his initial reason for coming to Silver City was to punish Jordan, who was inadvertently responsible for the death of Tin Man's family years ago, but now he realises that revenge is no longer worth it ("Listen to the Rain"). During an argument about Jo's refusal to send Tin Man away, Sara admits to Jordan why she married him ("When You Love Someone" Reprise). Tin Man sees through Jo’s disguise, and they reach out to each other, ending Jo's long denial of her true self ("Unbuttoning the Buttons"). Jo's desire to protect Tin Man becomes more important to her than hiding the truth.
As the town’s hostility rises to fever pitch, Sara discovers a letter from Jo’s son that contains a picture of her as a young woman. Realizing that Jo has deceived her for 18 years, Sara shows Jordan the picture and it ends up in the hands of the mob. Learning that Jo, like the mining company, has lied to them, the mob mindlessly heads for her cabin with torches, now looking for both Jo and Tin Man. Jo sends Tin Man to safety, assuring him that she will follow. When Sara arrives to tell Jo the mob knows her identity, Jo sends Sara home and faces the mob dressed as a woman ("Finale - Part 1"). A torch is thrown, and she is engulfed in flames ("Finale - Part 2"). Days later, Jo's son arrives in time for her funeral, and the townsfolk, shattered by the collapse of their silver dreams and the consequences of their actions, prepare to move on again ("Finale – Part 3").