Chandler graduated from George Walton Academy in nearby Monroe, Georgia in 1983. As a freshman at Walton, he was a member of the 1979 state championship football team. He left the team the following year, aged 14, after his father died of a heart attack. He participated in the theatre program at Walton after quitting football.

After graduating from high school, Chandler attended the University of Georgia, where he was a drama major and member of the class of 1984 Sigma Nu fraternity. In 1988, seven credits short of a bachelor’s degree in drama, Chandler dropped out of college to pursue a television deal.

In 1988, Chandler was signed by the American Broadcasting Company and brought to Hollywood as part of ABC’s new talent program. He made his television film debut that same year as a supporting hero actor in Quiet Victory: The Charlie Wedemeyer Story. Also in 1988, Chandler studied with acting teacher, Milton Katselas. His first major acting experience was a supporting role on television as Army Private William Griner in Tour of Duty. In eight episodes of the last season of the series, he played a member of a special operations squad fighting in Vietnam.

Chandler made his film debut in one of the key roles in the 1992 George Strait film, Pure Country. From 1991 to 1993, he had a series regular role as Cleveland Indians right fielder Jeff Metcalf in the ABC series Homefront, a drama set in the post-World War II era in the fictional town of River Run, Ohio. Homefront ran for two seasons, with Chandler appearing in all 42 episodes.

In 1994, he made his Broadway debut, co-starring with Ashley Judd, in a revival of William Inge’s Picnic at the Roundabout Theatre Company. From 1996 to 2000, Chandler starred as the lead character in the CBS series Early Edition, as a man who had the ability to change future disasters. He portrayed bar owner Gary Hobson, a stockbroker turned hero who received “tomorrow’s newspaper today”, delivered to his door by a mysterious cat. In 1996, he received the Saturn Award for Best Actor on Television for his portrayal of Hobson. Chandler was featured in all 90 episodes of the series, which ran for four seasons. In 2001, he appeared opposite Joan Cusack as investment banker Jake Evans in one season of the ABC comedy series What About Joan.

In 2003, Chandler played scheming lawyer Grant Rashton in six episodes of the short-lived NBC series The Lyon’s Den, opposite Rob Lowe. Working again in film, Chandler played the 1930s film star Bruce Baxter in the 2005 film King Kong (the character was based on romantic film star Bruce Cabot, who played Jack Driscoll in the original King Kong). Coincidentally, Chandler later played John Driscoll in The Day the Earth Stood Still.

While working on his Primetime Emmy Award-nominated guest role in Grey’s Anatomy, Chandler met Peter Berg, who was developing a drama series Friday Night Lights, which followed the lives of a high school football coach, his family, and the players in a small Texas town. The series was inspired by Buzz Bissinger’s book and the film of the same name. Chandler learned that he had been cast as high school football coach Eric Taylor when he was on Christmas vacation in 2005 with his family.

In February 2006, Chandler returned to television to guest star as the ill-fated bomb squad leader Dylan Young in two episodes of the ABC series Grey’s Anatomy. The episodes, titled “It’s The End of The World” and “As We Know It”, followed the Super Bowl XL. He received substantial praise for his performance and was nominated for the Outstanding Guest Actor in a Drama Series category at the 58th Primetime Emmy Awards. He appeared again on Grey’s Anatomy, in the February 15, 2007 episode “Drowning On Dry Land”, and the February 22, 2007 episode “Some Kind of Miracle”.

The show’s pilot aired on NBC in 2006. While critically acclaimed, the series was at risk of cancellation each year. Starting with the third season in 2008, first-run episodes of the show were broadcast on DirecTV satellite channel The 101 Network before being repeated on NBC. The final season ended in 2011.

While shooting the series, Chandler also acted in some films. In 2007, he appeared in The Kingdom, which was directed by Friday Night Lights creator Berg, and in 2008, he appeared in The Day the Earth Stood Still as John Driscoll.

After Friday Night Lights ended, Chandler focused on film work. In 2011, he had a lead role in J.J. Abrams’ science fiction film Super 8. The following year, he appeared in Argo. Chandler also co-starred in Kathryn Bigelow’s Zero Dark Thirty in 2012, playing the role of Joseph Bradley, an Islamabad CIA Station Chief. He co-starred alongside Jessica Chastain and Jason Clarke.

In 2013, he had a supporting role in Broken City, starring Mark Wahlberg, Russell Crowe, and Catherine Zeta-Jones. Chandler appeared in The Wolf of Wall Street, also released in 2013, based on the memoir of Wall Street tycoon Jordan Belfort. It was nominated for five Academy Awards including Best Picture. The film stars Leonardo DiCaprio and Jonah Hill, with Martin Scorsese directing. Chandler played FBI agent Patrick Denham. That same year, he played a deadbeat alcoholic father in The Spectacular Now.

For nearly 20 years after beginning his acting career in the late 1980s, Chandler lived in Los Angeles. Since 2007, Chandler and his family have lived on a 33-acre spread in Dripping Springs, Texas, southwest of Austin, where they own several dogs and donkeys. Chandler’s mother came to live with the family toward the end of her life, when she was living with Alzheimer’s disease. She died in 2014.

In 2015, Chandler co-starred in Todd Haynes’ drama film Carol, portraying “a jealous husband” to his wife played by Cate Blanchett, who is revealed to be lesbian. Also in 2015, Chandler returned to television with the Netflix drama series Bloodline, for which he was nominated for a Primetime Emmy Award. The show premiered to positive reviews from critics, and ended after airing its third season. In the 2016 drama Manchester by the Sea, he played the main character’s older brother.

In 2019, he starred in Godzilla: King of the Monsters, a role he is set to reprise in 2020’s Godzilla vs. Kong.