Rebecca Wolff was born in 1967 in New York City to Pamela Perry Wolff, of Nashville, Tennessee, and Anthony Wolff, a native of Brookline, Massachusetts who was raised on the Upper West Side of Manhattan. Her older brother is Nic Wolff. Rebecca and Nic attended the Fifteenth Street School, a "free" school based on A. S. Neill's Summerhill School in Suffolk, England, until 6th grade. Rebecca went on to Friends Seminary for middle school, and then to Stuyvesant High School. She published her first poem at the age of 15, in Seventeen Magazine, and her next soon after in the journal Hanging Loose's special section for high school age writers.

Wolff spent her first one and a half years of college at Bennington, in Vermont, majoring in Poetry, dropping out during the Field Work Term of her sophomore year, while she was interning at David R. Godine publishers. She stayed in Somerville, Massachusetts for a year and a half and worked the first of many jobs in the health food industry. Eventually Wolff finished her undergraduate degree at the University of Massachusetts at Amherst, attaining a Bachelors Degree with a Special Concentration in Poetry and Self-Consciousness in 1991. Her final year of undergraduate study was spent in Glasgow, Scotland, at the University there, though much of her time was spent hitchhiking around Europe, protesting the Gulf War as a member of the Socialist Party, and re-foresting the moorlands as a member of the "Green Group." Upon her return to the United States Wolff traveled to Iowa, where she attended the Iowa Writers Workshop, from which she received her MFA in Poetry in 1993. Wolff then spent several years living in Truro, on Cape Cod, and working at another health food store. She next moved to Houston, Texas, where she entered the MFA program in Fiction, but only stayed a year. While in Houston Wolff was employed as managing editor of the journal Gulf Coast, and it was this experience that allowed her to think that she would be able to organize her own literary journal, which she began doing upon her return to New York City in 1997.

In the spring of 1998 Fence was launched, with a crew of founding coeditors including Caroline Crumpacker, Jonathan Lethem, Frances Richard, and Matthew Rohrer. The next nine years of Wolff's life were devoted to publishing the journal, and also to Fence Books, launched in 2001, in a fairly typical "labor of love" style. During these years Wolff found paying gigs at the Poetry Society of America, BOMB magazine, and as a freelance editor for publications such as BookForum and PenguinPutnam. In 2001 her first book of poems, Manderley, was published by the University of Illinois Press, after having been selected for the National Poetry Series by Robert Pinsky. In June, 2002 Wolff married the novelist Ira Sher, and their son Asher Wolff was born in August. In September of 2004 Wolff's second book of poems, Figment, was published by W. W. Norton as a winner of the Barnard Women Poets Prize, and in December Margot Sher was born. In the summer of 2005 the family relocated permanently to Athens, New York, a river town in the Hudson Valley. In 2007, Fence and Fence Books found sponsorship at the University at Albany, in partnership with the New York State Writers Institute, of which Wolff is now a Program Fellow.