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.

The largest portion of the Mexican art collection is the retablos collection, which includes works from the 17th to the 20th centuries, the majority of which are by anonymous artists. In 2007 the El Paso Museum of Art was given seventy-nine retablos by the Frank and Sara McKnight family, enlarging that collection to over 550 works. 

The Mexican collection includes artworks from the pre-Revolution period by artists such as Auguste Lohr and Pablo Fischer, artworks from the Mexican Renaissance by artists such as Jean Charlot, Diego Rivera and José Clemente Orozco, and from the Rupture Generation by artists such as José Luis Cuevas, Manuel Felguérez, Teódulo Rómulo and Rufino Tamayo. 

More recent additions to the Mexican collection have included paintings, sculpture, prints, photography and video by artists such as Vladimir Alvarado, Francisco Castro Lenero, Felipe Ehrenberg Enriquez, Fermin Gutierrez, Leonardo Nierman, Gabriel Orozco, Carla Rippey, Vicente Rojo, Maria Sada, Oswaldo Sagástegui, and Saulo Cisneros.