His first major acting role was in the 1992 film Spotswood, alongside Anthony Hopkins, Ben Mendelsohn, Russell Crowe and Toni Collette. Later in 1992, he played neo-Nazi skinhead Cackles in Romper Stomper alongside Crowe, who got Wyllie his first agent. He counts Actress Toni Collette as a close friend, and appeared with her in the films Muriel's Wedding and Così.
In 2003 he appeared in the almost Long take video clip for The Sleepy Jackson Good Dancers (2003).
Wyllie's television work includes Bastard Boys, Bad Cop, Bad Cop, Underbelly and The Code. From 2005 – 2007, he had the role of Charlie Jackson in the drama series Love My Way, for which he received a Silver Logie for "Most Outstanding Actor in a Drama Series" in 2004. He also received Australian Film Institute Awards nominations in 2005, 2006 and 2007.
In 2010, he appeared in the role of Ezra White (one he had previously played in short drama film Ezra White, LL.B.), the central family's Lawyer, in the Australian crime drama Animal Kingdom.
In 2011, Wyllie joined the cast of Tangle as a guest star playing Michael Chubievsky in series three.
In 2012 he appeared in Puberty Blues in the role of Roger Knight and in The Straits as Jojo.
In 2013, he appeared in Rake (third series) as Cleaver's sensitive cell mate, Mal, who fears release.
In 2016 he appeared in Foxtel's political thriller, Secret City as Mal Paxton, a minister in the Australian Government.
