He is known for playing Captain Ronald Speirs on the 2001 HBO miniseries Band of Brothers and Rufus Humphrey on the CW teen drama series Gossip Girl.

[2] Settle made his Broadway debut in a strictly limited engagement in Chicago: The Musical, appearing as Billy Flynn from April 19 through June 13, 2010.

[3][4] He made his feature film debut in I Still Know What You Did Last Summer co-starring alongside Jennifer Love Hewitt, Freddie Prinze Jr., Mekhi Phifer, and Brandy Norwood.

From 2007 to 2012, Settle portrayed Rufus Humphrey, the father of Dan and Jenny, on the CW teen drama series Gossip Girl.

In 2007, Settle revealed that in 2006, at age 37, he had eloped to marry Israeli actress and model Naama Nativ,[2] with whom he had a child, born in 2009.