In February and March 1890, Smith College Professor J.H. Pillsbury organized several meetings for interested Northampton citizens on the work of the Young Men's Christian Association. Within a month, prominent local men, including C.H. Lyman, A.L. Williston, George Washington Cable, and F.N. Kneeland, established an Executive Board and committees with representatives from all the Protestant churches to raise funds and secure a building to begin the Northampton YMCA. By December, the Executive Board had leased the Smith Charities Building to start gymnasium classes, and in January 1891, Thomas Johnson was hired as the first general secretary. Incorporation followed shortly thereafter, in January 1892.

In the first decade, the YMCA established a Boy's Department under the direction of Robert L. Williston, started a Women's Auxiliary, and began a building fund that resulted in the purchase of property from A.L. Williston on King Street at "a nominal sum". The building, costing $30,500, was dedicated on October 15, 1904. By 1912, the YMCA had also raised an additional $25,000 for its summer camp, Nonotuck.

Throughout its history, the YMCA responded to local needs during periods of crisis or transition. During World Wars I and II, it established recreation programs for factory workers and soldiers stationed in the area. In 1942-44, the Hampshire YMCA became heavily involved in U.S.O. work, and, in the post-war era, developed programs with low-cost membership dues for returning servicemen. In 1936, the YMCA helped organize local flood relief, and during the depression it served as headquarters for the National Youth Administration. Similarly, the YMCA adapted to new groups in the area. In the 1920s it changed membership requirements to meet the needs of new immigrant groups entering Northampton and Easthampton to work in local factories. In the 1950s and 1960s, the YMCA began special programs on civil rights and desegregation.

Cutbacks in support from the Northampton Community Chest in the 1950s resulted in a decline in service in the post-war era. In 1960 the YMCA even considered a merger with the People's Institute. When the proposed merger collapsed, however, the YMCA established a new building fund drive that revived the Association and allowed it to build a more modern facility on Prospect Street at a cost of approximately one million dollars in 1966.

Over the years, a number of prominent local figures have played a role in the Hampshire Regional YMCA's history. Calvin Coolidge, George Washington Cable, and A.L. Williston were among the early board members. Robert L. Williston served on the board for nearly forty years, and Oliver L. Bradley for 36. Errol V. Ridgwell directed the YMCA's activities through four decades, serving as Executive Director from 1943 through 1969.

Records of the Hampshire Regional YMCA document the organization from 1891 to 1978. Materials include minutes, reports, board correspondence, program files (1937-1970), ledgers, publications and scrapbooks. Records were maintained by the various Executive Directors.

The papers occupy approximately 11.25 linear feet, and are divided into five series, including Administration (1891-1978), Reports (1908-1978), Correspondence (1923-1978), Programs and Activities (1937-1967), and Publications, Ledgers, and Scrapbooks (1912-1969).