Rhys Coiro grew up in Washington D.C. and he was born to Italian Albanian parents. He has a brother, Alec. He graduated with a BFA from the Carnegie Mellon University School of Drama. He attended Princeton High School in Princeton, New Jersey. Rhys Coiro has a daughter (born in 2008) by director Kat Coiro.

Coiro has appeared as recurring characters Billy Walsh on Entourage and Vincent Bianchi on Ugly Betty.

He portrayed FBI Agent Sean Hillinger in the seventh season of 24 on FOX. In the fall of 2008, Rhys began starring in Howard Korder's Boys' Life at Second Stage Theatre in New York City. Coiro played Paul in 2010's "30 Days of Night: Dark Days" and has a major role in the Straw Dogs Remake.