In 2006, Jesse guest starred in an episode of Law & Order portraying the character Kwame. He starred in the Off Broadway hits The American Dream and The Sandbox at Cherry Lane Theatre in Greenwich Village in New York City. Both one-act plays were written and directed by legendary playwright Edward Albee.
In 2008, Jesse made his theatrical debut in the supporting role of Leo in The Sisterhood of the Traveling Pants 2, a sequel to the 2004 film The Sisterhood of the Traveling Pants. He also starred as Drew Collins in a recurring role on the ABC Family series Greek, in which he appeared in two episodes.
In 2009, he portrayed Keya in the HBO pilot The Washingtonienne which was executive produced by Sarah Jessica Parker. The pilot however, was not picked up. He also signed on as Eddie Quinlain in the film Brooklyn’s Finest which stars Don Cheadle, Richard Gere, Ethan Hawke, Wesley Snipes and Ellen Barkin. The film was released on Friday, March 5, 2010. He also starred in an 8-episode stint in the television series Beyond the Break as Eric Medina.
In 2008, Jesse signed on in his first leading role as Holden McCrea in the MGM/United Artists Horror film The Cabin in the Woods. The film will be produced by Joss Whedon and directed by Drew Goddard. The film will be released January 14, 2011 and will be featured in 3-D.
In 2009, Jesse appeared in a multi-episode arc on the Golden Globe Award Winning ABC television series Grey’s Anatomy. He portrays a new Mercy West surgeon Dr. Jackson Avery in the series sixth season. He made his debut in the season’s fifth episode which aired October 15, 2009. On June 8, 2010, it was announced that Jesse had been officially upgraded to a full-time series regular, starting in season 7.
Jesse has modeled for Kenneth Cole. He also appears in the limited-edition coffee table book About Face by celebrity photographer John Russo.
He can also be seen as the love interest of R&B singer Rihanna in the music video for her single “Russian Roulette” from her 2009 album Rated R.