John C. Reilly may be the ultimate partner in crime, but he’s no second fiddle.

After co-starring in a number of famous two-handers and taking on memorable supporting roles, the veteran actor knows how to make being one-of-two work to his advantage. This year alone, Reilly has been one half of four duets — in his first Western, The Sisters Brothers, opposite Joaquin Phoenix, reprising his role as Wreck-It Ralph in Disney’s Ralph Breaks the Internet, reteaming with Will Ferrell for Holmes & Watson and co-starring as comedy legend Oliver Hardy of Laurel & Hardy in Stan & Ollie, for which he was recently nominated for both a Critics’ Choice Award and a Golden Globe.

“If you are in a partnership then it’s like 50 percent less work,” Reilly explains with a chuckle during a sit-down with ET. “Also, if you really mess up, it’s only 50 percent your fault. These are all the benefits of having a partner. I’ve had a lot of brother relationships in my life — partnerships and collaborations with people — so I really understood that kind of intense one-on-one partnership with somebody.”

One of Reilly’s most famous partnerships is with Ferrell. The pair has proven to be one of the great comedy duos of the 2000s, having teamed up for Talladega Nights and Step Brothers ahead of this month’s Holmes & Watson, in which Ferrell stars as Sherlock Holmes and Reilly as John Watson. Though it’s been 10 years since Step Brothers, Reilly says fans still constantly come up to him to talk about Dale and Brennan.

“It seems like yesterday we shot that movie,” he recalls. As for why the comedy has proven so special, Reilly says it’s because it’s more than just a funny movie. “There’s some real stuff in there. There is some real subversive detail about family relationships…and what it’s like being in a divorced family or a blended family.”

For nearly three decades, Reilly has put his whole heart into acting, boasting over 100 screen credits and an Oscar nomination for his supporting role in Chicago. “When I was younger, before I was getting offered larger roles, being someone’s buddy, that’s a time-honored entry point for character actors in the movie business,” he recalls. “You might not be the main guy, but you’re the best friend and that’s a pretty good gig.”

By embracing the idea that he wouldn’t always be the lead, Reilly has been able to carve a path in Hollywood that is as varied as it is successful. He is one of a few working actors who books dramatic roles as regularly as he books comedies, who can dive into both tent-pole movies and animated tales. “You can make all the choices you want in terms of the kind of roles you want to play,” he says. “But if the audience is not interested in seeing you play those roles, well, then you’re going to have a pretty short career.”

“Luckily for me, if there’s one through line through my whole career, it’s that I’m doing really different things,” he continues. “Different genres in comedy and drama and action movies. Now that I’ve done a Western, I think I’ve covered them all, including space movies and the rest. So, I feel really lucky in that way that audiences are willing to take a gamble with me each time and see what I’m going to do.”

Now, Reilly is taking a moment to take in the celebration of his work. “The fact that people are noticing my performance and the films, in general, is the best case scenario,” he says with a grin. “That’s what you’re hoping for. You’re hoping for a miracle.”