The Kalamazoo Chamber of Commerce traces its beginnings to the Press Club which formed to bring a new state normal school to the city. After its success, it became the Kalamazoo Chamber of Commerce, later known as the Kalamazoo County Chamber of Commerce and eventually the Kalamazoo Regional Chamber of Commerce. Over the years to fulfill its mission to attract and support businesses and a business agenda, the Chamber spearheaded various programs and other activities which their members participated including the Northside Business Alliance, the Environmental Commission, Leadership Kalamazoo, New Year’s Fest, the Transportation Commission, Poverty Reduction and Public Policy. They also were involved with Kalamazoo Communities in Schools and the Kalamazoo Area Academic Achievement Program. The organization also investigated the idea of a unified government structure which they called Metropolitan Government. They also created the Kalamazoo County Convention and Visitors Bureau which later separated from the Chamber and is now known as Discover Kalamazoo.

In 2013, the Chamber was merged with Southwest Michigan First.