In the 16th century, Spanish explorers became the first Europeans to enter park area. Further exploration and eventual settlement took place in 19th-century as the Southwest became U.S. territory. Homesteaders arrived in the park in the late 1800s, attracted by the grasslands on which cattle could graze. Grazing occurred until the 1950s and some ranches remain outside park boundaries.
The park features several sites that are listed on the National Register of Historic Places and one National Historic Landmark (the Painted Desert House Inn)