The Society bought a vacant building in Balboa Park in 1917 left over from the 1915 Panama-California Exposition. Finally owning sizable space to create a proper museum, the Society formally changed its name to the San Diego Natural History Museum and was able to grow its collections and library holdings. After moving between three buildings in Balboa Park, the museum finally commissioned architect William Templeton Johnson (by now well known in the area for designing other impressive museums) to build them a permanent home. Even with a substantial contribution of 125,000 from Ellen Browning Scripps, the museum failed to raise the full amount needed for the project, due largely to the challenges of the depression era. Thus, only part of the originally planned museum was built before the museum formally opened in 1933, with two of the exterior walls left plain as temporary walls to be finished later when the museum finished its expansion. Those temporary walls ended up remaining for nearly 60 years, until a massive 32 million dollar plan was commenced in 1992 that led to massive expansion of the museum. By 2002, the renovation was completed, leaving the San Diego Natural History Museum over twice the size of its previous structure.
A tumultuous moment in the museum's history came during World War II, when the U.S. Navy conscripted the building for use as a military hospital. The museum was forced to hastily pack up its massive collections, dispersing them throughout 32 locations, while the library relocated to San Diego State College. Meanwhile, the new use of the building required the installation of an elevator to transfer patients from different areas and a nurses' station in-between floors of the museum-turned-infectious-disease-ward. Interestingly, both additions remain today.