The oldest part of the DePue House was probably built around 1870 by Isaac Peiser. The Blair family became owners in 1900 and expanded it to its present size in 1903.

During the 1930's, Grace Blair DePue built a two-story, brick building behind the house for her collection of North American Indian artifacts. Upon her death in 1944, the collection of 2,831 items was willed to the University of California at Berkeley.

The house is now a private residence not open to the public.