He gained wider recognition for his starring role in the Insidious film series (2010–2023) and as Ed Warren in The Conjuring universe (2013–present), both horror franchises.

[8] In 1999, he starred as Jamie Conway in the off-Broadway production of Bright Lights, Big City, and Wilson later made his Broadway theatre debut in The Full Monty (2000), portraying Jerry Lukowski.

[19] The following year, he starred alongside Elliot Page in the psychological thriller film Hard Candy, portraying a pedophile named Jeff Kohlver.

[21] Also in 2006, he appeared in the Golden Globe Award-nominated Running with Scissors as Michael Shephard, which was directed by Ryan Murphy and produced by Brad Pitt.

[25] Wilson played the primary antagonist Lynch in 2010's The A-Team, and co-starred with Rose Byrne in James Wan's horror film Insidious.

[26] In 2013, Wilson portrayed the famous paranormal investigator Ed Warren, alongside Vera Farmiga starring as his wife Lorraine, in the horror film The Conjuring.

[29] In January 2014, Wilson was announced to portray the lead role, Lou Solverson, in the second season of FX's anthology series Fargo.

[34] In August 2016, Barbra Streisand released the album Encore: Movie Partners Sing Broadway, on which she and Wilson duet the song "Loving You" from the Stephen Sondheim musical Passion.

[36] Also that year, he portrayed Orm Marius / Ocean Master in the DC Extended Universe film Aquaman, directed by long-time collaborator James Wan.

On November 8, 2019, Roland Emmerich's World War II film Midway, was released, starring Wilson along with Ed Skrein, Mandy Moore, Luke Evans, Aaron Eckhart, Nick Jonas, Dennis Quaid and Woody Harrelson.

[46][47][48] He also contributed vocals to the end credits song "Stay" on the film's soundtrack, collaborating with Swedish metal band Ghost, who he is a fan of.

In April 2012, Wilson gave the keynote address for his alma mater, Carnegie Mellon University, in which he spoke of his memories from childhood and through his career.