Wenham started his career as an actor after graduating from Theatre Nepean at the University of Western Sydney in 1987 where he studied under Terry Browne. Wenham's television credits include several telemovies, such as his AFI award winning role in the 1996 telemovie Simone de Beauvoir's Babies; and his role as the outwardly laid back but deeply enigmatic diver Dan Della Bosca in the 1998 and 1999 seasons of the highly successful ABC television series SeaChange. His role as "Diver Dan" has made the actor something of a sex symbol, although he dislikes thinking of himself as such, and he has been voted Australia's "sexiest man alive". A portrait of Wenham by artist Adam Cullen won the Archibald Prize in 2000. Wenham is signed to Storm Model Management in London.
He was also seen in Van Helsing playing Hugh Jackman's sidekick, Friar Carl. His character, Dilios, narrated and appeared in the movie 300. Minor roles of Wenham's in overseas films include in The Crocodile Hunter as a park ranger, and briefly in Moulin Rouge! as Audrey. Wenham stars in the music video for Alex Lloyd's single "Brand New Day". In 2008's Australia, he reunited with Hugh Jackman playing antagonist Neil Fletcher who seeks to acquire the ranch Jackman's character is employed with.
In both Lord of the Rings: Return of the King and 300, Wenham's character is the sole survivor returned from an ill-fated battle (the Battle at Osgiliath and the Battle of Thermopylae, respectively). He reprises his role of Dilios in the videogame 300: March to Glory for Sony PlayStation Portable, which contains a substantial amount of new dialogue.
In 2010, Wenham starred as the disgraced Melbourne Lawyer Andrew Fraser in the Australian TV series Killing Time. This 10 part series shows Fraser's fall from grace as he defends many Melbourne criminals during the 1980s and 1990s. It was shown on TV1 in late 2011.
Key: (a)= Winner of Best Performance by an Actor in a Leading Role in a Mini Series (b)= Best Actor in a Actor in a Leading Role in a Telefeature (c)= Best Performance by an Actor in a Leading Role, in a Mini-Series or Telefeature (d)= Best Actor in a Leading Role in a Television Drama or Comedy (e)= Best Lead Actor in Television All other names, which aren't marked with a letter next to their name, have won the current Lead Actor in a Television Drama award.