Howe was born in Boston and grew up in nearby Cambridge. Her mother, Mary Manning, was Irish and wrote plays and acted for the Abbey Theatre. Her father, Mark DeWolfe Howe, was a professor at Harvard Law School. Her sister is the poet Fanny Howe. Howe graduated from the Boston Museum School of Fine Arts (1961). She was married to the painter, Harvey Quaytman. She was married to her second husband, sculptor David von Schlegell, until his death (1992). Her third husband, Peter Hewitt Hare, a noted philosopher and Professor at the University of Buffalo, died in January 2008. She has two children, the painter R.H. Quaytman, and the writer Mark von Schlegell. She lives in Guilford, Connecticut and was a Fall 2009 Anna-Maria Kellen Fellow at the American Academy in Berlin, where she is working on her newest poetic sequence A Collection of Poems and Essays.

Howe is author of a number of books of poetry, including Europe of Trusts: Selected Poems (1990), Frame Structures: Early Poems 1974-1979 (1996) and The Midnight (2003), and two books of criticism, The Birth-Mark: Unsettling the Wilderness in American Literary History (1993) and My Emily Dickinson (1985). Her work has appeared in numerous anthologies, including The Norton Anthology of Modern and Contemporary Poetry, and the important Language School gathering of poets: In the American Tree (edited by Ron Silliman).

In 2003, Howe started collaborating with experimental musician David Grubbs. The results were releasedon two CDs: Thiefth (featuring the poems Thorow and Melville's Marginalia) andSongs of the Labadie Tract.

Her main literary influences are Dickinson, Charles Olson and early Puritan writers like Cotton Mather, as well as minimalist artists such as Agnes Martin and historians such as Richard Slotkin. The link between these is New England, and Howe can be viewed as a New England poet in her sense of new possibilities and preference for an economy of means. Recent writings, including Pierce-Arrow (1999), reflect an ongoing dialogue and engagement with the writings of Charles Sanders Peirce.

Howe spent some time in Dublin, where she worked as an actor and assistant stage director with the Gate Theatre. She paints and has worked as a radio producer. Since 1989 she taught English at the University at Buffalo, The State University of New York until she retired in October, 2006.