The EPMA’s collection of American art begins with significant examples of Colonial portraiture such as Gilbert Stuart’s c. 1796 Portrait of George Washington, as well as portraits by Jacob Eichholtz, Charles Loring Elliot, Rembrandt Peale and Thomas Sully. 

The El Paso Museum of Art has collected the work of living artists since its establishment. The Museum's holdings include works across a range of media.

From International Gothic through the Realism of the 19th century the El Paso Museum of Art’s European collection includes masterworks by artists such as: Bernardo Bellotto, Sandro Botticelli, Canaletto, Jusepe de Ribera, Lavinia Fontana, Artemesia Gentileschi, Lorenzo Lotto, Bartolome Esteban Murillo, Hyacinthe Rigaud, Anthony van Dyck and Francisco Zubarán. 

The El Paso Museum of Art’s Mexican collection includes paintings on panel, canvas, copper and tin from the Spanish Viceroyal period.  Starting in 1660 with an oil on canvas painting of The Flagellation of Christ by an anonymous Mexican artist, many of the artworks from the next two centuries were created for use as devotional images. Representative artists from this period that are included in the collection are Miguel Cabrera, Nicolás Enríquez, Antonío de Torres, Francisco Martínez, and Juan Sánchez Salmerón, among others.