He got into acting during his first few years at the University of Virginia, and moved to Los Angeles in late 2001 to look for acting opportunities. While in New York he appeared off-Broadway in Life is a Dream at the SoHo Rep. Additionally, he performed in numerous productions at the Williamstown Theatre Festival, including Street Scene and The Blue Bird, and at the University of Virginia in Measure for Measure and Zoo Story. He then moved to Los Angeles, where he landed a lead role in The O.C.
August 05, 2003, FOX premiered the television series The O.C., about affluent teenagers with stormy personal lives who reside in scenic Orange County, California. The show became an overnight success and it put McKenzie on the map as Ryan Atwood. McKenzie's performance in The O.C. earned him a "Choice Breakout TV Star - Male" and "Choice TV Chemistry" nominations in The Teen Choice Awards and a "Choice TV Actor - Drama/Action Adventure" and "Choice TV Actor: Drama" wins.
As a result to the show's success, McKenzie appeared in magazines including People, In Touch Weekly and Us Weekly. McKenzie was ranked No. 5 in Independent Online's "100 Sexiest Men Alive", was twice placed on Teen People magazine's annual list of "25 Sexiest Stars under 25". He was also voted one of InStyle's "10 Hottest Bachelors Of Summer" in July 2005. The O.C. dropped in ratings dramatically during its third and fourth seasons, and ended in early 2007.
While appearing in 'The O.C.', McKenzie made his feature film debut in Junebug alongside Amy Adams and Embeth Davidtz. The film was nominated for "Best International Film" and "Outstanding Ensemble Acting" in The Amanda Awards and won the Sarasota Film Festival award for "Outstanding Ensemble Acting". It also received high praise at the 2005 Sundance Film Festival. He also appeared in a pivotal role in the 2007 film 88 Minutes, which starred Al Pacino. According to Production Weekly, McKenzie was set to star in the thriller Snakes On A Plane, formerly known as Pacific Air 121, but later dropped out to film 88 Minutes.
In 2008, McKenzie earned critical acclaim for his solo performance in the "live on stage, on film" version of Dalton Trumbo's 1939 novel Johnny Got His Gun, his first starring role in a feature film. He stars as Joe Bonham, a role previously played by James Cagney, Jeff Daniels, and Timothy Bottoms. The movie premiered at the Paramount Theater in Austin, TX, McKenzie's hometown, while he was filming the pilot for Southland.