The Bedford-Stuyvesant YMCA was founded in 1888, with its first home located at 420 Gates Avenue. At the time, the Bed-Stuy community was one of the fastest-growing in Brooklyn, and the facility soon outgrew its space. Construction on the new branch building, located on the corner of Bedford Avenue and Monroe Street, began in 1901 and was completed in 1905. This multi-story brick building featured state-of-the-art facilities including: gymnasium, swimming pool, auditorium, classrooms, and traditional rooms for rent. In 1919 an annex was built to expand the branch's trade school teaching programs, with auto repair, aviation, and other growing trades being taught. These programs became a major part of the Bed-Stuy Y's offerings through the 1970s.

In 1976 the branch discontinued all adult programs due to a decline in membership, but undertook a major renovation to house an alcoholic treatment center funded by the City's Health and Hospitals Corporation and Model Cities. In 1991 the branch revived its youth program, and in 2007 the branch underwent a major renovation and expansion of the existing 41,000 square-foot facility. 

In 2009, the Bedford-Stuyvesant Y was the first branch to receive the YMCA of Greater New York's Janice Reals Ellig Transformational Leadership Award. This distinction, awarded during the YMCA of Greater New York's annual General Assembly, is only occasionally bestowed upon YMCA branches that have successfully achieved a positive, sustainable outcome that contributes in a major way to the Y's vision for New York City.