The museum was a 20-year dream for Carmella Hudson, a WWII nurse–turned–school teacher. In 1993 she began to build the collection, pulled together a board of directors and established the non-profit corporation. GHM first opened to the public at 106 Trade Street on September 11, 1996. It soon moved to the Bailes-Collins building at 208 Trade Street and stayed there a decade, gradually building a strong collection of artifacts and documents.

In late 2007 it became clear the museum would need to find a new home; while in a temporary location at 215 Trade Street (now Cartwright Food Hall), the museum worked with the City to settle permanently in the historic 1935 Greer Post Office. After a building renovation, director Joada Hiatt organized and displayed the collection in the new location; it opened in 2008. Joada retired in 2015, and the museum entered a period of decline. In 2021 a revitalization of the museum began, including new exhibits, events and collection care; David Lovegrove was named executive director.

In 2025 the museum began a major renovation of the building and core exhibits. In October 2025, it launched the Greer Historical Society.

Today the museum is thriving, with record attendance and donations, and leading the celebration of Greer's sesquicentennial, our 150th anniversary. GHM has become an integral part of the cultural fabric of Greer, and looks forward to sharing Greer’s amazing story with you!