Born in Brookline, Massachusetts, into a wealthy and distinguished New England family that included the poet James Russell Lowell, she grew up in an intensely intellectual atmosphere. Inspired by a performance by the actress Eleonora Duse in 1902, Amy Lowell began to write poetry. Her first book, A Dome of Many-Colored Glass (1912), was fairly conventional, but in 1913 she fell under the influence of Ezra Pound and his new school of imagism. From this time on she devoted her life to writing and publicizing the new poetry.

Lowell's first book to contain imagist poetry was Sword Blades and Poppy Seeds (1914). It was followed by Men, Women, and Ghosts (1916), which includes her celebrated poem “Patterns,” dramatizing the frustrating restrictions that senseless tradition puts on life and art. Later collections of verse included Can Grande's Castle (1918), Legends (1921), and What's O'Clock (1925), for which she was awarded a Pulitzer Prize. Lowell experimented with many forms, including Chinese and Japanese, but her most successful poems centre on American themes.

Her critical studies were also well received. In Six French Poets (1915) she translated and discussed the work of her French contemporaries, while in Tendencies in Modern American Poetry (1917) she publicized the imagist cause and the work of her fellow American poets. Her other works include A Critical Fable (1922), which was modelled on James Russell Lowell's A Fable for Critics, and a biography of John Keats (1925).