His well-received guest appearance on the medical drama Grey's Anatomy (2006–2007), earned Chandler his first Primetime Emmy Award nomination.

Chandler's film work[2] has included notable supporting roles in King Kong (2005), The Day the Earth Stood Still (2008), Super 8 (2011), Argo, Zero Dark Thirty (both 2012), The Wolf of Wall Street (2013), Carol (2015), Manchester by the Sea (2016), Game Night and First Man (both 2018), Godzilla: King of the Monsters (2019), Godzilla vs. Kong (2021).

[10] She "was highly active with the Great Dane Club of America (GDCA) as a breeder, judge and championship prize winner.

[14][10] 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.

[16] He made his television film debut that same year as a supporting hero actor in Quiet Victory: The Charlie Wedemeyer Story.

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.

[8] In 2003, Chandler played scheming lawyer Grant Rashton in six episodes of the short-lived NBC series The Lyon's Den, opposite Rob Lowe.

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.

[21] 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.

[21][23] 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.

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.

'"[26] Chandler won the Primetime Emmy Award for Outstanding Lead Actor in a Drama Series for his role in the final season of Friday Night Lights.

Chandler also co-starred in Kathryn Bigelow's Zero Dark Thirty in 2012, playing the role of Joseph Bradley, an Islamabad CIA Station Chief.

[17] 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.

[38] He portrayed Silicon Valley investor Bill Gurley in Showtime's Super Pumped alongside Joseph Gordon-Levitt.