The Regional Municipality of Hamilton-Wentworth was proclaimed by the Progressive Conservative government of Ontario on January 1, 1974 (with legislation being passed the previous year).

Regional municipalities were an experiment in two-tier municipalities created from the late 1960s to the mid-1970s (mainly in the Golden Horseshoe of southern Ontario but also in Sudbury in northern Ontario and Ottawa in eastern Ontario). It proved somewhat controversial and H-W was one of the last created by this process. Almost from its creation, some sort of merger was advocated, with "Wentworth" among the candidates for the new megacity.

The H-W first-tier municipality comprised the bulk of the former Wentworth County which it replaced. Its second-tier municipalities were, in order of population, the City of Hamilton, the Town (in 1984, the City) of Stoney Creek, the Town of Ancaster, the Town of Flamborough, the Town of Dundas and the Township of Glanbrook.

The region provided police services, public transit and social services, while the second-tier provided fire services and recreation services. Both shared respoinsibility for roads and water.

It was governed by a regional chair who presided over a regional council comprised of representatives of each of Hamilton's wards and two each from other constituent municipalities. Near the end of its existence, the regional chair was chosen by direct election.

A different Progressive Conservative government amalgamated all of H-W's contituent municipalities into the larger singe-tier City of Hamilton in 2001, against great opposition from its suburban and rural parts. This was part of a broader series of municipal reorganizations of urban and rurual Ontario, which also affected the former Municipality of Metropolitan Toronto, the Regional Municipality of Ottawa-Carleton, Chatham-Kent and Prince Edward County, among many others.