Mabel Loomis was born 10 November 1856 in Cambridge, Massachusetts, the daughter of Eben Jenks Loomis, an astronomer and mathematician, and Mary Alden (Wilder) Loomis. She was educated in private schools in Washington, DC and Boston, and married David Peck Todd in 1879. After her husband's appointment as professor of astronomy and director of the observatory at Amherst College in Massachusetts, the couple traveled around the world to study eclipses of the sun and other phenomena. On Todd's first trip to Japan she became the first woman to climb Mount Fuji. She went on to write several well-received books on astronomy and became a noted lecturer on that topic.

In Amherst, Todd taught at private schools for young women, participated in church events, and helped to organize civic and literary groups, such as the Amherst Historical Society, the local chapter of the Daughters of the American Revolution, and the Boston Authors' Club. She also became friends with William Austin Dickinson, brother of Emily Dickinson and the Amherst College treasurer. Publicly the two worked together to preserve the town's natural environment; privately they engaged in a thirteen year long affair while remaining married; apparently their spouses knew of the relationship. After Austin's death, his wife Susan successfully challenged his will, which left a major bequest to Mabel.

When Emily Dickinson died in 1886, over 1700 manuscript poems were discovered in her house. Todd began the arduous task of deciphering the handwriting, collating the variants, arranging the poems chronologically, and transcribing them for publication. She published two series of Dickinson's poems with Thomas Wentworth Higginson in 1890 and 1891, and a third series on her own in 1896. Mabel Todd was responsible for bringing the first volumes of Emily Dickinson's verse to the reading public, but her estrangement from the Dickinson family following Austin's death in 1895 forced her to postpone work on the remaining poems. Todd's daughter Millicent Todd Bingham drew upon her editorial work when she published her own edition of Dickinson's poems, Bolts of Melody, over a decade later.

In 1913 Todd became partially paralyzed, but in the last nineteen years of her life she continued to be culturally and socially active in Miami, Florida, where she wintered. She died in 1932 of a cerebral hemorrhage.

Her papers are in the Boston Public Library.