The Puerto Rican star picked up an Oscar award for best supporting actor for his role in Traffic, and was nominated again in 2003 for his turn in 21 Grams.
He is already receiving heavy buzz for his portrayal of revolutionary leader Che Guevara in Che, a film that has already won him best actor at the 61st Cannes film festival, and reunited him with his Traffic colleagues - director Steven Soderbergh and producer Laura Bickford.
Yet he prefers to blow off any talk of awards, saying: "I just got lucky, you know. My guess (about the forthcoming awards) is as good as yours."
The 41-year-old says it was sheer good luck that lead to his involvement in the two-part biopic, which he also co-produced.
"Why did I have to play him? I don't know," Benicio admits.
"I just got lucky. I thought this could be an interesting story - it's got so many dimensions. I've always been a fan of underdogs, and I think that in a way, he was an underdog.
"There's something about that that I've been attracted to. I don't know why. And I think that Che had elements of that. He never really quit. In the end, he's like an underdog and for me, the fact that he was executed kind of also put a flame that this story should be told."
And he insists that he is merely portraying his interpretation of Che.
"I knew a little about him but I didn't know much about Che. I'm making an interpretation as other actors can make an interpretation of him," he says.
"So it's Benicio Del Toro doing interpretations of moments of Che Guevara - it's my interpretation of this character."
While admitting that his preparation to play the Argentine Marxist guerrilla leader was exhausting, Benicio claims he didn't feel added pressure to portray him in the 'right' way.
"The process of playing Che was very different for me than other movies I have made," he says.
"I like to quote what Steven said to me - that I was like a deer in headlights. He said, 'it's impossible to play him or to do this film, but we'll try'. And that was very liberating.
"The other thing is, you do all the research you do. In this case, as a real person, you start with the man himself and what he wrote. This led us to seven years of research into what other people wrote about him. Even so, I always returned to what he had written himself.
"It's a learning process and it can be a lot of fun. We got lucky, meeting a lot of people who knew him and spent time with him all the way to October 8, 1967, the day before he was executed. Meeting those people, reading what he wrote, there's many photographs, there's footage of him, and then you put all that together - but then at some point, you have to throw it away.
"You can't go with this pre-conceived idea of what you're going to do in every scene that you might be able to do in other movies. Here, you want to react more than act, so in a way you're playing defence more than offence. In order to do that, you have to throw everything away that you learnt, trust it and bring in yourself in a way. It's kind of like 'pack your bags' and then, don't worry if you lose it."
One of the things he wanted to show was that Che was vulnerable.
"I think one of the things what showed him as human was his asthma and being a sick man," he says.
"It's easier to play vulnerability. If it was in the scene, then you would just play it. That's it. I'm an actor, so vulnerability isn't that hard to do."
Even so, the filming schedule was a challenge for the seasoned actor.
"It was long and exhausting and we shot in five different countries. So it was like a touring band who was moving from Spain to Puerto Rico to New York to Mexico to Bolivia," Benicio recalls with a grimace.
He drew strength from interest in the iconic figure.
"Every time I went south of New York City, for years before we even shot anything, people would come up and say, 'Oh, a Che Guevara movie. It's great!' like they had already seen it," he admits.
"I remember being in an airport in Buenos Aires and someone said, 'Oh, a Che Guevara movie. It's great!' and we hadn't even shot anything. I don't think we even had a script.
"So the movie was basically taking over in a way. We had to find a way to do it. So in a way, the movie kind of like was already in motion before we even stepped on the gas. That added pressure to it."
He may play a political leader, but Benicio is eager to steer away from political talk about Latin America.
"We could sit down and talk about that and political statements I'm not allowed to talk about because I'm not a political figure," he says, with a smile.
"I'm not really qualified to discuss what is going on in particular with these leaders."
BENICIO DEL TORO - EXTRA TIME
Benicio (Beno) was born to lawyer parents and grew up in Santurce, Puerto Rico, but moved to Pennsylvania when he was 13.
He had small TV parts in the late 80s, playing mostly thugs and drug dealers. While he appeared in Madonna's La Isla Bonita video, his breakout performance was in The Usual Suspects as the mumbling wise-cracking Fred Fenster.
In 2001, Benicio won a best supporting actor Oscar for Traffic, becoming the third Puerto Rican actor to win an Oscar.
The eligible bachelor keeps his love life under wraps although he previously dated British star Claire Forlani, French actress Chiara Mastroianni, and was engaged to Italian actress Valeria Golino. He was also rumoured to have had a close encounter with Scarlett Johansson in a lift.
Che Part 1: The Argentine was released on Friday January 2. Che Part 2: Guerrilla will be released on Friday February 20.