The youngest of seven, Wenham was raised in Marrickville, Australia and received his training at the University of Western Australia. He first caught notice in his native land with a part on the popular primetime serial "Sons and Daughters" in the 1980s. After honing his craft on stage (including a well-received turn in the searing play "The Boys" in the early 1990s), Wenham moved into films with a bit role in "Greenkeeping" (1992). When he reprised his stage role as a pyromaniac in "Cosi" (1996), the actor began to receive critical praise and attention beyond his native land. Recreating another stage role, this time the sociopathic Brett Sprague, an ex-con who returns home with unpleasant consequences in Rowan Woods' realization of "The Boys" (1997), Wenham solidified his status as a major star in Australia, earning nominations for several prizes including the Australian Film Institute Award with his brilliant turn as the troubled, nasty and dysfunctional parolee. Although the film received international distribution, US audiences avoided the piece, missing a chance to see the actor's fine work.

Adding to his cache, Wenham became a reluctant sex symbol in 1998 when he was cast in the Australian Broadcasting Company's weekly series "SeaChange,” playing the scruffy 'Diver Dan' who comes to romance a female judge (Sigrid Thornton) over the course of twenty-six episodes. His work on the series brought the actor many magazine covers and a nomination for an Australian Film Institute Award.

When he departed the series, Wenham accepted the lead role in the biopic of the Belgian priest who spent his life at a leper colony in Hawaii in "Molokai: The Story of Father Damien" (1999), which premiered at the Toronto Film Festival. The movie, however, was adversely affected by disputes between the director and producers so few had a chance to enjoy Wenham's fine performance. That fate didn't befall his brief turn as a transvestite playwright in Baz Luhrmann's kaleidoscopic "Moulin Rouge!", although his chameleonic abilities made him difficult to recognize as the same person portraying the straying Jewish spouse in "Russian Doll,” the swaggering international photojournalist enjoying a one-night stand in "better than sex" or the cowboy turned soldier in "Dust" (all released in 2001 in the USA). Wenham caught the eye of mainstream audiences with an appearance in "The Crocodile Hunter: Collision Course" (2002) opposite real-life wildlife expert Steve Irwin, and received major exposure when he took on the role of Faramir for parts two and three of director Peter Jackson's adaptation of J.R.R. Tolkein's "Lord of the Rings" trilogy.

In the Australian-made gangster comedy “Gettin’ Square” (2003), Wenham was a drug addict trying to go straight while working at a restaurant with two ex-con buddies (Sam Worthington and Timothy Spall), only to find himself in trouble with the law once again when they decide to take down a local crime boss (Gary Sweet). After playing the dedicated friar sidekick in “Van Helsing” (2004), Wenham took a dramatic turn in “Three Dollars” (2005) as an honest and compassionate man who finds himself supporting a wife and child with only three dollars to his name. He served as the catalyst for bloodshed in John Hillcoat’s gritty western “The Proposition” (2006), playing an arrogant and brutal lawman who beats the younger brother (Richard Wilson) of an outlaw (Guy Pearce) sent by a British captain (Ray Winstone) to murder his eldest and more dangerous brother (Danny Houston). In “300” (2007), the adaptation of Frank Miller’s graphic novel about the famed Battle of Thermopylae in 480 B.C., Wenham played a one-eyed warrior named Dilios who tells the tale of King Leonidas (Gerard Butler), leader of the 300 Spartan warriors who fought to the death when holding off a massive Persian army lead by Xerxes I (Rodrigo Santoro).