Woolson never married, and though most of her closest friends and correspondents were men, there is no indication of a romantic interest in any of them. But unlike her friends Katherine Loring and Alice James, who shared one of the most famous "" of the era, Woolson never entered into a female partnership either.

Daughter of Charles Jarvis Woolson and Hannah Cooper Pomeroy, and grandniece of writer James Fenimore Cooper, Constance Fenimore Woolson was born on March 5, 1840 in Claremont, New Hampshire. After suffering the loss of three young daughters to scarlet fever the year of Constance's birth, the family moved to Cleveland, Ohio. There, Woolson was educated at Miss Hayden's school and the Cleveland Female Seminary. She later went to Madame Chegary's School in New York City, graduating in 1858.

Little is known of Woolson's life during the Civil War, but she spent time in Cleveland and New York and worked for the Union cause. In 1870 and1871 she wrote travel sketches about New York for the Daily Cleveland Herald. Beginning in 1873, she moved South, traveling with her mother through Pennsylvania, Virginia, the Carolinas, Georgia, Kentucky, Tennessee, and Florida. She left for Europe in November 1879 following Hannah Woolson's death.

Though she had planned to retire in St. Augustine, Florida, Woolson never returned to the United States. She traveled extensively throughout Europe and the world, visiting Austria, Germany, Switzerland, the Greek Islands, and Egypt, but she lived primarily in Florence and Venice, where she was a neighbor, for a short time in 1883, of John Addington Symonds, an art critic and outspoken defender of homosexual rights.

Woolson died in 1894 from injuries she sustained after falling from a balcony in Venice. Contemporary newspapers and a letter by James indicate that she probably committed suicide. Throughout her life, Woolson suffered from long periods of depression and isolation due to a hearing impairment that brought on increasing deafness.

Scholarly interest in Woolson's work, particularly her short fiction, has grown significantly in recent years. Feminist critics have focused on her strong female protagonists, especially artists, and on her ambivalence toward heterosexual love and marriage. Scholars of the U. S. Civil War and Reconstruction have admired her depictions of the post-war South, some of the first and best produced by a Northern woman.

Woolson published widely in the periodicals of the day, but her first two short story collections, Castle Nowhere: Lake-Country Sketches (1875) and Rodman the Keeper: Southern Sketches (1880) earned her respect as a serious regionalist writer among contemporary critics, including James. Her novels include Anne (serialized in1880; published as a book in 1882), For the Major (1883), East Angels (1886), Jupiter Lights (1889), and Horace Chase (1894). Two other story collections, The Front Yard and Other Italian Stories (1895) and Dorothy and Other Italian Stories (1896), were published posthumously.

Woolson's fiction frequently depicts intimate relationships between women, often with an undercurrent of , but two stories in particular, "Felipa" and "Miss Grief," appear to address the issue of female homosexuality directly.

"Felipa" is the story of a boyish twelve-year old Minorcan girl who develops an obsessive crush on a beautiful woman named Christine, who is vacationing in Florida with her friend Catherine, a painter. The young girl becomes a double for Catherine, who also seems to have romantic feelings for Christine but represses them. Lillian Faderman suggests that "Felipa may be seen as a subtle meditation on the connection between romantic friendship and sexual inversion."

Indeed, Karl Ulrich's pamphlets on "Urnings" (individuals who have a female mind trapped in a male body or vise versa) and Karl Von Westphal's writing on "contrary sexual feeling" had been published in Germany in the mid-1860s, and the character of Felipa does seem to reflect this new discourse to a large extent. However, the story indicates that Felipa has been raised almost entirely by men, suggesting that her masculine tendencies may not be entirely inborn. Thus, Woolson also appears to meditate on the degree to which gender and sexuality are inborn or socially constructed.