Born in Fall River, Massachusetts, Mary Macomber achieved a reputation for her Pre-Raphaelite style of allegorical painting. In Fall River, she studied still life painting with Robert Dunning and then spent a year at the Boston Museum of Fine Arts School. Illness prevented her from continuing there, but later she studied in Boston with Frank Duveneck.
In 1903, much of her work was lost in a studio fire. She also had poetry talent, and a book of her poetry was published in 1914. From 1890 to 1903, she exhibited at the National Academy of Design, and from 1895 to 1903 in nine annual exhibitions of the Art Institute of Chicago.