Byrne graduated from Boston College with a double major in finance and theater, and later earned an M.F.A. from the Theater School at DePaul University. He is from Old Tappan, NJ and attended Northern Valley Regional High School at Old Tappan.

His film credits include lead roles in Final Destination 5 as Isaac Palmer and Horrible Bosses opposite Jennifer Aniston, Jason Bateman, and Jamie Foxx. He also starred in Dinner for Schmucks, Extraordinary Measures, Charlie Wilson's War, Bruce Almighty, and Fun with Dick and Jane.

Byrne's on-camera television credits include a series regular role as Irv Smiff, a driven sports agent, on BET's The Game and guest appearances on The Mentalist, Castle, It's Always Sunny in Philadelphia, Burn Notice, Bones, Desperate Housewives, New Adventures of Old Christine, NCIS, The West Wing, and ER.