Born in Ohio, he went to Southeastern High School, South Charleston, and later studied acting at New York's HB Studio.

Chambers gained widespread recognition as the series progressed and the character became one of the most popular from the hit series, earning multiple nominations and the 2017 Best TV Network Drama Actor at the People's Choice Awards as well as nominations for the Screen Actors Guild Award.

[5] Chambers was discovered by a modelling scout on the Paris Metro and went on to star in advertising campaigns for Calvin Klein's fragrance range.

He worked throughout Europe, Japan, and the United States for Calvin Klein, Armani, and Dolce & Gabbana.

In 2003, Chambers was cast as one of the leads in the CBS crime drama Cold Case but left after appearing in only three of the show's first four episodes.

In August 2004, Chambers was cast as surgical intern Alex Karev in Shonda Rhimes's medical drama series Grey's Anatomy, opposite Ellen Pompeo, Sandra Oh, Katherine Heigl, and T. R.

In 2022, Chambers played actor Marlon Brando in the Paramount+ series The Offer, a biographical drama about the production of The Godfather.

[13][14] Chambers is involved with the nonprofit organization Pentecostal Christian Church mission Dream Center of Los Angeles.