Work in films followed, beginning with his debut in Big Top Pee-wee (1988) and as Dario in the James Bond movie Licence to Kill (1989), in which the 21-year-old del Toro held the distinction of being the youngest actor ever to play a Bond henchman.
Del Toro continued to appear in movies including The Indian Runner (1991), China Moon (1994), Christopher Columbus: The Discovery (1992), Money for Nothing (1993), Fearless (1993) and Swimming with Sharks (1994).
During his acceptance speech for the Best Actor's trophy at the Screen Actors Guild Awards, Penn expressed his dismay stating, "The fact that there aren't crowns on Soderbergh's and del Toro's heads right now, I don't understand...
that is such a sensational movie, Che." In September 2015, del Toro played Alejandro Gillick in the critically acclaimed Sicario, about a principled FBI agent who is enlisted by a government task force to bring down the leader of a powerful and brutal Mexican drug cartel. In 2016, del Toro appeared in a Heineken beer television advertisement in its More Behind the Star series. '" In an interview with The Times, he mentioned that he did not want his West Hollywood apartment, which he described as his "cave", to be "invaded" by a wife and children.
As Javier Rodriguez — a Mexican border policeman struggling to remain honest amid the corruption and deception of illegal drug trafficking — del Toro, who spoke most of his lines in Spanish, gave a performance that dominated the film.
His performance swept all of the major critics' awards in 2001.
His career gained momentum in 1995 with his breakout performance in The Usual Suspects, where he played the mumbling, wisecracking Fred Fenster.
The role won him an Independent Spirit Award for Best Supporting Male and established him as a character actor.
Del Toro won an Academy Award for Best Supporting Actor, becoming the fourth living Oscar winner whose winning role was a character who speaks predominantly in a foreign language.
Del Toro is also the third Puerto Rican actor to win an Oscar, after Jose Ferrer and Rita Moreno.
In 2008, del Toro was awarded the Prix d'interpretation masculine (or Best Actor Award) at the Cannes Film Festival for his characterization of Che Guevara in the biographical films The Argentine and Guerrilla (together known as Che).