Much of Elizondo's theology focuses on the theological significance of the mestizo/a and the process of mestizaje, which he defines as a mixing of two or more groups of people, biologically, culturally, and/or religiously. He is most interested in the position of Mexican-Americans, whom he regards as the product of a double process of mestizaje, the first being the biological, cultural, and religious mixing that created the Mexican people and the second being the primarily cultural mixing between Mexicans and Anglos in the U.S. Southwest. This second mixing occurred originally through U.S. expansion and conquest of formerly Mexican territory and has continued through Mexican immigration to the U.S. Elizondo believes that the position of the mestizo/a puts him/her in a unique position as both insider and outsider. From this unique position, the mestizo/a has the potential to help bring about a new, united humanity. Elizondo writes, "With each new mestizaje, some racio-cultural frontiers that divide humankind are razed and a new unity is formed." Elizondo is also interested in the Virgin of Guadalupe as symbol of the Mexican people and therefore as a product of the process of mestizaje.

English-language works by Elizondo include the following:

• Galilean Journey: The Mexican-American Promise
• Christianity and Culture: An Introduction to Pastoral Theology and Ministry for the Bicultural Community
• Guadalupe: Mother of the New Creation
• The Future is Mestizo: Life Where Cultures Meet
• God of Incredible Surprises
• Beyond Borders: Writings of Virgilio Elizondo and Friends (with Gustavo Gutierrez and Timothy Matovina)
• San Fernando Cathedral: Soul of the City (with Timothy M. Matovina)
• Mestizo Worship: A Pastoral Approach to Liturgical Ministry (with Timothy M. Matovina)
• Mestizo Democracy: The Politics of Crossing Borders (with John Francis Burke)
• Our Lady of Guadalupe: Faith and Empowerment among Mexican-American Women (with Jeanette Rodriguez)
• Way of the Cross: The Passion of Christ in the Americas (with John Drury)

He received his B.S. degree from St. Mary's University, a Diploma in Pastoral Catechetics from the East Asian Pastoral Institute, his M.A. from Ateneo University, and his S.T.D. and Ph.D., from the Institut Catholique de Paris in 1978.