Born in Florence, Alabama, Hoffleit earned an undergraduate degree in mathematics from Radcliffe College in 1928 and a doctorate in astronomy from Radcliffe in 1938. At age 23 she joined the American Association of Variable Star Observers and began working as a research assistant at Harvard College Observatory under Harlow Shapley. She calculated missile trajectories during World War II and eventually joined the astronomy department at Yale, where she remained until her official 1975 retirement, although she continued to work daily from her office until well into her 90s.
Among her many achievements, she was the author of the Bright Star Catalogue, a compendium of information on the 9,110 brightest stars in the sky; she co-authored The General Catalogue of Tirgonametric Stellar Parallaxes, containing precise distance measurements to 8,112 stars, information critical to understanding the kinematics of the Milky Way Galaxy and the evolution of the solar neighborhood. In 1988, Hoffleit was awarded the George Van Biesbroeck Prize by the American Astronomical Society for a lifetime of service to astronomy.
She also wrote Sky & Telescope magazine’s news notes from its second issue in 1941 until the mid 1950s, with ad-hoc contributions until 1997. She also helped and encouraged young women pursuing astronomy, training college undergraduates during summer months from 1957 to 1978 at the Maria Mitchell Observatory in Massachusetts.
The oldest astronomer to ever live, she died at age 100 in March 2007, having published her autobiography, Misfortunes as Blessings in Disguise, five years previously.