He became widely known after his appearance on The WB singing competition show Popstars 2, where he was one of the winners selected to be a member of the pop group Scene 23.

He later played main roles in the horror films Fingerprints (2006), and April Fool's Day (2008), as well as in the romantic comedy The Jerk Theory (2009).

From 2006 to 2007, Henderson co-starred in the ABC comedy-drama series Desperate Housewives as Austin McCann, the nephew of the character Edie Britt, played by Nicollette Sheridan.

[12] In February 2011, Henderson landed a lead role in the TNT revival of the CBS prime-time soap opera Dallas.

[21] Henderson dated singer Ashlee Simpson from 2002 to 2003,[22] former reality show participant Kendal Sheppard from 2006 to 2007, actress Brittany Snow from 2007 to 2008, and television personality Andrea Boehlke from 2013 to 2016.

[citation needed] On December 12, 2018, LA police arrested Henderson on suspicion of having broken into his neighbor's house earlier that day.

[23] TMZ reported that Henderson had an airtight alibi for the night of the robbery at his neighbor's home, as he provided security footage that allegedly shows he never left his apartment.