Serna's first break in movies came in 1970 on the Roger Corman-directed film The Student Nurses. Over the years, Serna has appeared in over 100 films. In the blockbuster comedy The Jerk, he appeared as a lowrider-driving criminal who cons a naive Steve Martin out of money and new tires. Another notable role was in Scarface, directed by Brian De Palma, as Tony Montana's friend Angel Fernandez. Serna played the charismatic guru Nanak in Aguruphobia, which he also co-produced. He has also appeared on stage, including his solo show El Ruco, Chuco, Cholo, Pachuco.
Serna has been honored by the Screen Actors Guild Heritage Achievement Award; the League of United Latin American Citizens, and the Estrella Award for Arts & Culture from the Orange County Hispanic Chamber of Commerce. Serna played Señor Cárdenas in the film Downsizing.
^ ab"Pepe Serna (visual voices guide)". Behind The Voice Actors. Retrieved June 20, 2024. A green check mark indicates that a role has been confirmed using a screenshot (or collage of screenshots) of a title's list of voice actors and their respective characters found in its opening and/or closing credits and/or other reliable sources of information.