Harriet was raised as a boy by her physician father in Watertown, Massachusetts. Dr. Hosmer had lost his wife and other children to tuberculosis and thought that only the vigorous exercise common to boys could fortify his daughter against disease. He encouraged Hattie's interest in riding and shooting and encouraged her art by allowing her to set up her first studio on the family property.
Harriet's behavior was considered scandalous. Her mannish dress and outgoing, casual conduct were entirely uncommon among women in her genteel circle and inspired gossip. With a great sense of adventure, she traveled the Mississippi without a chaperone. She explored mines and won a footrace up a high bluff against several young men. The bluff, near Lansing, Iowa, was christened Mt. Hosmer and still bears that name.
One of Harriet's early works, Hesper, the Evening Star (1852), came to the attention of Boston actress Charlotte Cushman, a lesbian famous for playing "breeches" or men's parts, who was preparing to move to Rome. Knowing that most American art schools either refused to admit women or charged them more in tuition than men, Cushman convinced Harriet's father to allow her to move to Rome and live under her care.
Once in Rome, Harriet was apprenticed to English sculptor John Gibson. Cushman's circle of friends consisted of mostly "emancipated" women, and the younger Harriet quickly became a key figure in this world of creative and intellectual excitement.
Harriet's abrupt personality sparked a great deal of discussion. She had no patience for the strict rules of decorum that regulated behavior among young ladies in polite circles of her day. Instead, she was driven to work long hours in the studio, perfecting her art.
Harriet was an admitted flirt. She shared a close relationship with her boarding school friend Cornelian Crow, who eventually became her biographer; but her most intense relationship was with Louisa Ashburton, a widowed Scottish noblewoman. The two shared finances and wrote intimate letters in which Hosmer used the term "wedded wife" in reference to herself.
Although intense friendships among women were common, Hosmer dropped her characteristic joking voice in many of the letters to Ashburton while speaking of devotion and also jealousy at the thought of being replaced by another woman.
Harriet eventually returned to America, where she was welcomed as a celebrated artist. She worked on inventing a perpetual motion machine before her death in Watertown.