The house was built in 1880 to serve as the manse of Knox Presbyterian Church. Malcolm Bethune became the minister of Knox Church in 1889 and, a year later, his son Norman was born there. The Bethune family remained in Gravenhurst until 1893 when they moved to Beaverton, Ontario. Thereafter, the house was occupied by a succession of ministers.
In 1973 Bethune Memorial House was purchased by the Department of External Affairs on behalf of the Government of Canada. Restoration of the building was subsequently undertaken by Parks Canada, which is now responsible for its operation.