The Mission Inn's story spans over a century, beginning with the Miller family, who moved to Riverside, California, from Tomah, Wisconsin. In 1874, civil engineer Christopher Columbus Miller arrived in Riverside and, with his family, opened a small boarding house. His son, Frank Augustus Miller, purchased the property in 1880 and began expanding it. Collaborating with architect Arthur Benton and backed by railroad tycoon Henry Huntington, Frank was inspired by Mission Revival architecture and California’s growing tourism scene. In 1903, he opened the first wing of what would become the Mission Inn. Over time, the building evolved through several phases, each reflecting contemporary architectural styles and Miller’s travels through Europe and Asia. By 1931, the Mission Inn occupied an entire city block, with four wings, gardens, towers, and a vast collection of global art and artifacts.

After Frank Miller’s death in 1935, his family managed the Inn until selling it in 1956 to hotelier Benjamin Swig. Attempting to revive its appeal, Swig sold off much of the Inn's art and redecorated it in modern styles, but the effort failed to restore its former popularity. The Inn declined through a series of owners and was even converted into dorms and apartments.

Concerned locals founded the Friends of the Mission Inn in 1969 to protect the building and its contents. The City of Riverside bought the property in 1976, and in 1977, the Inn was designated a National Historic Landmark, recognizing its cultural and architectural significance.

In 1985, the Inn was closed for a planned $50 million renovation by a private developer. Despite near completion in 1988, bankruptcy stalled progress until 1992, when Riverside entrepreneur Duane Roberts acquired and reopened it. Community efforts and private investment make the Mission Inn a preserved and celebrated historic landmark.