In the late 1960s McAllen’s Junior League negotiated an agreement with the city for a 5,000-square-foot building, soon to be home of the International Museum of Art and Science. The League, determined to provide citizens of the Rio Grande Valley with educational, and meaningful, access to the arts and sciences, established the museum to promote their mission. The museum and its collection opened to the public on October 26, 1969. Less than a decade later the museum had outgrown its facilities, constructing its current building as part of McAllen’s Bicentennial Project in 1976.

Today, the museum exhibits its permanent collection of Folk art, with emphasis on the folk arts of Texas and Mexico, alongside its selections of decorative and fine arts, as well as its examples of geology and the earth sciences. The museum also presents special exhibits throughout the year including an interactive display exploring the region's watershed, and a state-of-the-art exhibit designed by NASA and the National Oceanic and Atmospheric Administration called “Science On a Sphere”. In its art galleries, the museum hosts exhibits featuring work by significant regional and international artists.