Benjamin McKenzie Schenkkan was born in Austin, Texas. He is of Dutch-Jewish, English, and Scottish descent. He is one of three boys born to Frances Victory Schenkkan, a poet, and Pieter Meade "Pete" Schenkkan, an attorney. His middle name, McKenzie, is his paternal grandmother's maiden name. His grandfather, Robert F. Schenkkan, was a professor at the University of Texas at Austin, and worked with President Lyndon B. Johnson on passing the Public Broadcasting Act of 1967. He is a nephew of Pulitzer Prize-winning Playwright Robert Schenkkan, Jr.

For middle school, he attended St. Andrew's Episcopal School, where he was friends and flag football teammates with Future Super Bowl MVP Drew Brees. He attended Stephen F. Austin High School, playing wide receiver and defensive back for the school's football team. From 1997–2001, he attended the University of Virginia, his father and paternal grandfather's alma mater, where he majored in foreign affairs and economics. He uses his middle name as his stage name to avoid confusion with actor Ben Shenkman.

From 2001 to 2003, McKenzie worked in part-time jobs and sought acting work in New York and Los Angeles before being cast as Ryan Atwood in The O.C. On August 5, 2003, Fox premiered the television series, about affluent teenagers with stormy personal lives in Orange County, California. The show became an overnight success and made McKenzie famous. His performance in The O.C. earned him "Choice Breakout TV Star - Male" and "Choice TV Chemistry" nominations in the Teen Choice Awards and "Choice TV Actor - Drama/Action Adventure" and "Choice TV Actor: Drama" wins. McKenzie reportedly earned between about $15,000 and $25,000 per episode throughout the show's run.

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. 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, which starred Al Pacino.

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, McKenzie's hometown, while he was filming the pilot for Southland.

McKenzie starred as rookie police officer Ben Sherman on the NBC drama Southland, which premiered on April 9, 2009. The show was canceled while in production on its second season. TNT bought the rights for the show and showed the seven episodes that had been produced. The show was subsequently renewed. However, the show was once again cancelled after the fifth season.

McKenzie returned to Fox in the Batman prequel television show Gotham, which premiered on September 22, 2014. In the series, he portrays James Gordon as a young detective new to Gotham City. In the same series, he made his directorial debut with the season 3 episode "These Delicate and Dark Obsessions". McKenzie went on to direct "One of My Three Soups" and write "The Demon's Head" from the fourth season.

In September 2015, Morena Baccarin said in a legal declaration involving her divorce that she planned to marry her Gotham co-star, McKenzie, adding that she was pregnant with their child. Their daughter Frances Laiz Setta Schenkkan was born March 2, 2016. Baccarin and McKenzie announced their engagement in November 2016. They were married on June 2, 2017 in Brooklyn, New York.