As part of promoting In the Land of Women, Milligan posted a series of eight video diaries on YouTube with the ostensible aim of obtaining a date for the film's premiere. Milligan appeared in the music video "Made in the USA" by Demi Lovato.
He is known for playing the role of Ethan Ward in The CW's 90210, a spin-off of the 1990s primetime drama Beverly Hills, 90210. He was written out of the show at the end of the first season.
His film credits include Final Destination 3 (2006), Slither (2006), The Butterfly Effect 2 (2006), In the Land of Women (with Kristen Stewart, Adam Brody and Meg Ryan), (2007), Butterfly on a Wheel (2007), The Messengers (2007) and Extract (2009).
Milligan starred in the short-lived primetime suspense drama Runaway, picked up by The CW for its inaugural season in September 2006, but cancelled in October after only three of nine episodes completed had been aired.
He starred in the Canadian network CTV's made-for-TV film Eight Days to Live playing O.C. star Kelly Rowan's missing son. Milligan has also played minor roles in the television series The Days, Andromeda, The Dead Zone, Alice, I Think, Supernatural, the CBC's Da Vinci's City Hall.
In 2010, Milligan starred as Kyle Halsted in the indie action crime drama film Repeaters co-starring with Amanda Crew. In 2011, he starred as Nick in the horror thriller shark movie Shark Night 3D. In 2011, he played the role of Nick Nader in the suspense thriller The Entitled and played the role of Rory in the indie film Sisters & Brothers. In 2012, Milligan starred as Sam Reed in the Lifetime Original Movie Love at the Christmas Table co-starring Danica McKellar. Milligan appeared in the Funny or Die video with Elisabeth Hower. In 2013, Milligan played the role of Callum Beck in the indie thriller Ferocious co-starring Amanda Crew.
In 2014, Milligan starred as Detective Reverend Grizzly Night-Bear in a vintage 70s"buddy cop" movie Bad City. Milligan played the role of John in the James Wan's directed horror film Demonic. In 2015, Milligan landed main role in spy thriller TV show X Company, where he plays the role of Tom Cummings, and he has a recurring role in Schitt's Creek, where he plays the role of Ted Mullens. He had a guest spot as Blaine in the TV show Silicon Valley. Later in 2015, Milligan had a lead role as Ogden in the indie drama Sequoia co-starring Aly Michalka.
In 2016, Milligan starred as Cory in the indie comedy film Me Him Her. The movie was written and directed by Max Landis. He starred as Nicholas Gray in the indie mystery thriller film Primary. Milligan is set to star in the film The Headhunter's Calling. He plays the role of aggressive young recruiter at Blackridge who’s training under Butler’s character. He played the role of Sgt. Hugo Friedkin, a dimwitted government agent working with Riggins, in the BBC America series Dirk Gently's Holistic Detective Agency.