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José Angel Santana began his acting career as a student of Sanford Meisner at The Neighborhood Playhouse. He has also studied, speech & voice with Julliard's Robert Neff Williams, script interpretation with Stella Adler, Improvisation with Paul Sills, Lee Strasberg’s method with MarIlyn Fried. He also studied with Mira Rostova.   

In 1978 he began acting Off-Off-Broadway in the role of Plato, in Rebel Without a Cause, followed by David Mamet’s The Blue Hour, alongside Patti Lupone Off-Broadway at the New York Shakespeare Festival, then with fellow beginner Denzel Washington in the Shakespeare in Central Park production of Coriolanus, starring Morgan Freeman. In 1980 he was cast in the Broadway production of Tony Award and Pulitzer Prize recipient, Howard Sackler's play Goodby Fidel.

Santana has originated leading roles in works by some of the most important international playwrights: three world premieres of his mentor David Mamet's plays: The Blue Hour, Edmond, and Mamet's adaptation of Anton Checkov's The Cherry Orchard with William H. Macy; in his friend Trevor Griffiths' play Real Dreams, opposite two-time Academy Award winner Kevin Spacey; in Eduardo Machado's The Modern Ladies of Guanabacoa, and in the title role of El Extensionista, Felipe Santander's Casa de Las Americas Award-winning play. 

​In film, José Angel Santana received critical acclaim for his heartbreaking debut performance as "José - the Junkie" in Sidney Lumet's Prince Of The City and is remembered as the "Strange Boutique Owner" with Madonna, in Susan Seidelman's ‘80’s cult classic Desperately Seeking Susan. These are among his many featured performances in film & television, which can be found here, (IMDb).​