Henrietta Leavitt was born in Cambridge, Massachusetts, the daughter of a Congregational minister. She attended Oberlin College and the Society for Collegiate Instruction of Women (later Radcliffe College). As a senior in 1892, Leavitt discovered astronomy. After graduation she took another course in it, but then spent several years at home when she suffered a serious illness that left her severely deaf. She hadn't forgotten about astronomy, though. She volunteered at the Harvard College Observatory in 1895. Seven years later she was appointed to the permanent staff (at a salary of 30 cents an hour) by director Charles Pickering. She got little chance to do theoretical work, but did become head of the photographic photometry department. This group studied photo images of stars to determine their magnitude.

During her career, Leavitt discovered more than 2,400 variable stars, about half of the known total in her day. These stars change from bright to dim and back fairly regularly. Leavitt's work with variable stars led to her most important contribution to the field: the cepheid variable period-luminosity relationship. By intense observation of a certain class of variable star, the cepheids, Leavitt discovered a direct correlation between the time it took a star to go from bright to dim to how bright it actually was. Knowing this relationship helped other astronomers, such as Edwin Hubble, to make their own groundbreaking discoveries.

Leavitt also developed a standard of photographic measurements that was accepted by the International Committee on Photographic Magnitudes in 1913, and called the Harvard Standard. To do this she used 299 plates from 13 telescopes and used logarithmic equations to order stars over 17 magnitudes of brightness. She continued refining and enlarging upon this work throughout her life.

Leavitt was not allowed to pursue her own topics of study, but researched what the head of the observatory assigned. Because of the prejudices of the day, she didn't have the opportunity to use her intellect to the fullest, but a colleague remembered her as "possessing the best mind at the Observatory," and a modern astronomer calls her "the most brilliant woman at Harvard." She worked at the Harvard College Observatory until her death from cancer in 1921.