Very much a go-to guy for director Paul Thomas Anderson, he took on meaty character roles in Magnolia, Boogie Nights and Hard Eight.
He also demonstrated his considerable acting chops in films such as The Perfect Storm, The Thin Red Line, Chicago, The Aviator and The Good Girl.
This was all before his second career incarnation, where Reilly began to evolve into a comedian.
Supporting roles in Talladega nights: The Ballad of Ricky Bobby and Tenacious D: the Pick of Destiny, led to a starring role in Walk the Line spoof Walk Hard: The Dewey Cox Story.
However, it was with his role in Step Brothers alongside Will Ferrell that he truly became comic royalty.
Not content with conquering the worlds of comedy and drama, Reilly — who dabbled in singing in Chicago and Walk Hard now intends to take on the world of music.
John C Reilly (alongside Beck Stark and Tom Brosseau) performs acoustic roots music with quite some distinction and is signed to Jack White’s Third Man Record Label.
On Tuesday, the A-list actor will play St Andrews in The Square, from 7.30pm. He said: “Roots music. It’s just another way of saying good old music that has survived the passing of time: folk, traditional, bluegrass, close-harmony, country.
“Whatever labels people have tried to stick to good music through the ages are irrelevant. It’s that song that touches something deeper, that makes ancient sense to your soul.
“The tree of music has deep roots which go back to these songs, conceived and sung around lonesome campfires, rain soaked ship’s decks, whispering mountain pines or dusty barren farmland they stand the test of time and keep our souls alive.”
To book tickets to see Reilly — who is a busy man at the moment with his Disney vehicle Wreck it Ralph set for release this week — visit www.synergyconcerts.com.