The Gallup Cultural Center has a rich history. The building is a two-story, stucco-clad building constructed in 1918 to serve as an area headquarters for the Santa Fe Railway, the successor to the Atlantic and Pacific Railroad. In 1923, an adjoining structure was built to house a famed Fred Harvey hotel and restaurant complex known as “El Navajo.” Designed by the company's Mary Colter, the hotel was dedicated during a ceremony that included a performance by local Navajo singers and “medicine men.” Much of the hotel portion of the building was demolished in 1957 to make way for a widening of U.S. Route 66.

The city of Gallup in partnership with the Southwest Indian Foundation renovated the old depot in 1996 in order to preserve it. This measure was successful, and the Gallup Cultural Center opened inside the depot that same year. In addition, the building serves as an Amtrak Station,  the Storyteller Museum and Gallery of the Masters; the Kiva Cinema, Enchantment Skate Shop, and Angela's Cafe.