While still a student, Dobrygin was cast as Dima Maykov in Producer Timur Bekmambetov's Black Lightning (2009), the first Russian-language blockbuster superhero film.

Dobrygin earned worldwide recognition after Director Alexei Popogrebsky spotted him at a theatre performance and ended up casting him in How I Ended This Summer (2010). Dobrygin and Sergei Puskepalis, the only other on-screen actor in the film, shared the Silver Bear for Best Actor at the 60th Berlin International Film Festival for their roles in the film, shot over three months at a meteorological station on an Arctic island in the Chukchi Peninsula. Dobrygin also won the Best Actor trophy at the 2010 Russian Guild of Film Critics Awards for his performance. Following his success; the media dubbed him "the most famous student in Russia."

In November 2013, he made his debut as a theatre Director at the Mayakovsky Theatre.

Dobrygin has stated his intent to return to the dancing world through a film project. He told The Guardian in October 2014, “Five years after I stopped dancing I thought about going back. Now it’s been 10 years, so it’s going to be a documentary experiment for me: I’m going to go deep into ballet, prepare my body and then travel the world with a professional coach, an international Choreographer and a camera.” In March 2015, he told Interview magazine, "I really want to go back on the big stage and dance something. I didn't finish my last year at the academy—I was not assigned to the theatre. And this was what was once the meaning of life: to dance."

In 2015, Dobrygin starred in an adidas commercial directed by Pharrell Williams, #OriginalSuperstar, along with Pusha T, Japanese designer Yoon, VJ/designer VJ Mian, and Mexican Illustrator Smithe.

In 2016, Dobrygin directed a short, Mind the Gap, featuring his A Most Wanted Man co-star Willem Dafoe. The short sold fore more than $100,000 for a children's charity.