Born on September 10, 1886, in Bethlehem, Pennsylvania, into a middle-class family of strong Moravian faith, Doolittle was the fourth of six children and only daughter of Charles Leander Doolittle, professor of mathematics and astronomy at Lehigh University (then University of Pennsylvania), and Helen Wolle Doolittle, manager of a chaotic household that paid great deference to the father.

She attended various private schools before she went off to Bryn Mawr for a year in 1905. Feeling an intellectual failure to her father and a social failure to her mother, the young H.D. left Bryn Mawr and looked for consolation in writing and reading Greek literature and in her engagement (disapproved of by the Doolittle family) to the upstart poet Ezra Pound, whom she had met in 1901.

She also sought for a "sister," and in 1910 found Frances Josepha Gregg, a kindred spirit and her first female lover. What ensued was a painful romantic triangle between Hilda, Frances, and Ezra, the emotional intensity of which H.D. never fully left behind. In its aftermath, H.D. sailed for Europe with Gregg and Gregg's mother, where she soon began in earnest her literary career.

Introduced into the literary avant-garde by Pound as "H.D., Imagiste," she wrote poetry in a style that was sparse, concrete, precise, and direct in its imagery. This style obeyed the "masculine" credos to pull poetry away from late Victorian, diffusive, sentimental, "feminine" writing. She stood out as a brilliant young writer of poetry undertaking radical innovations in language and rhythm in the name of modernism.

She met (and possibly had an affair with) Brigit Patmore, who in 1912 introduced her to Richard Aldington, free-lance writer and poet. H.D. said he was a man "who will make his way in the world, which I don't much like people to do." Their relationship ended after six years that included marriage, adultery, and the stillbirth of their child in 1915. When she left him, she began and quickly ended an affair with Cecil Gray, a musicologist briefly in her social circle, by whom she became pregnant.

H.D. had published at this point translations, her own Sea Garden (1916), and poems in little magazines and anthologies. Having read and admired the poet's work, a young woman who called herself Bryher (Annie Winifred Ellerman) sought her out, thus beginning their lifelong love and partnership. H.D. believed that Bryher saved her life when, soon after they met, Bryher helped nurse her through a dangerous influenza just before the birth of her daughter, Frances Perdita, in 1919.

Although the passion of their affair eventually lightened, H.D. still gave to Bryher the intensity she brought to everything in her life. They lived, worked, and traveled together for the next twenty-six years, and corresponded closely when they were apart. Bryher married twice for appearances, appeasing her extremely wealthy and influential English family, and H.D. had intermittent affairs; but the two remained deeply committed to each other for the rest of their lives.

H.D. never returned to live in the United States for any extended time; she divided her residence mostly between London and Switzerland, remaining a prolific and respected writer. After a stroke in June 1961, she died on September 27 at a Swiss clinic where Bryher cared for and comforted her.

During the modernist period, several lesbian writers produced and published works explicitly and implicitly exploring lesbian experience. H.D. kept her ties loose to these writers, who were mostly consolidated in Paris. Like them, however, she developed works that celebrated women's romantic relationships with each other. Her early poetry divulges her erotic attachments much more obliquely than her mostly autobiographical prose, which explores the complexity and depth of her feelings for women. Unfortunately, these prose novels were not published until after her death.

Three novels, composed in the 1920s, relate her creative, erotic, and emotional development as centered on passionate attachments to women, following many of the same events of her life while varying the details. As in Radclyffe Hall's The Well of Loneliness (1928) and Djuna Barnes's Nightwood (1936), lesbianism is central to the plots and conflicts of Paint It Today (1921), Asphodel (1921-1922), and HERmione (1926-1927).

Her poetry published at the time explores her often tormented heterosexual life; these manuscripts that she left unpublished disclose her homosexual life. For H.D., being out to the public was not only uncomfortable but risky. H.D. and Bryher downplayed their relationship by referring to themselves as "cousins."