Erected in 1938 for Hospital Co. 108, 103rd Medical Regiment, mustered into the Pennsylvania National Guard in 1925. The lot had been the site of the President's House, erected by Jefferson College about 1842. The armory is constructed in the Colonial Revival architectural style and is on the National Register of Historic Places. The Armory was closed in 2010 by a restructuring of the guard’s unit bases.
Members of the military assigned to the Canonsburg Armory were transferred to the new, $9.9 million, 38,000 square foot Waynesburg Readiness Center built on 18 acres at the EverGreene Industrial Park in Franklin Township, Greene County that was dedicated on August 26, 2010.