Born in Sanegerman, Puerto Rico, Del Toro grew tip in Pennsylvania. He attended the University of California at San Diego where he divided his time between painting and acting classes. He appeared in numerous student productions, one of which led to performing at a drama festival at the Lafayette Theater in New York. Del Toro remained in New York to study acting at the Circle in the Square Acting School and won a scholarship to the Stella Adler Conservatory in Los Angeles. He studied at the Actor's Circle Theatre, which led to guest staffing roles on various television series and movies for television.

Del Toro made his motion picture debut in the James Bond film License To Kill. He has been honored with back-to-back Independent Spirit Awards for Best Supporting Actor for his work in The Usual Suspects and for Julian Schnabel's Basquiat. Del Toro's other motion picture credits include Sean Penn's Indian Runner, John Baily's China Moon, Peter Weir's Fearless, George Huang's Swimming With Sharks, Abel Ferrara's The Funeral, Tony Scott's The Fan, Marco Brambilla's Excess Baggage and Terry Gilliam's Fear and Loathing In Las Vegas.