He is best known from his multiple stand up comedy hour specials; creating, writing, and starring in Sullivan & Son; and as the writer/director of the feature film The Opening Act.

In early 2011, he toured on The Comedy Road Show with Vince Vaughn and Kevin James to promote the film The Dilemma.

Byrne wrote and created with Rob Long the comedy Sullivan & Son on TBS that premiered in the summer of 2012.

Byrne spent the early part of 2018 directing a documentary about Las Vegas headliner, magician and comedian The Amazing Johnathan, entitled Always Amazin'.

[4] From 2017–2018, Byrne wrote a script while on the road about his early years in stand up comedy, which eventually became The Opening Act.

He has made appearances on Chappelle's Show, Tough Crowd with Colin Quinn, @midnight, The History Channel's "History of the Joke," Mad TV's 300th episode and Super Bowl promos on CBS with Prince and again with Bill Cowher.

His stand-up has been featured on The Late Late Show, Jimmy Kimmel Live!, Last Call with Carson Daly, BET's ComicView, ABC's Good Morning America as well as Comedy Central's Premium Blend.

He has opened for musical acts Kanye West, Mariah Carey on her Charmbracelet Tour, Modest Mouse, Puddle of Mudd, Spoon, Rev.

Byrne has toured with The Kims of Comedy with Bobby Lee of Mad TV and Ken Jeong of NBC's Community and The Hangover.