He is known for his roles as Faramir in The Lord of the Rings film trilogy, Friar Carl in Van Helsing and Van Helsing: The London Assignment, Dilios in 300 and its sequel 300: Rise of an Empire, Al Parker in Top of the Lake, Lieutenant John Scarfield in Pirates of the Caribbean: Dead Men Tell No Tales, and Hank Snow in Elvis.

His role as "Diver Dan" has made the actor something of a sex symbol, although he dislikes thinking of himself as such,[4] and he has been voted Australia's "sexiest man alive".

He reprises his role of Dilios in both the 2014 sequel, 300: Rise of an Empire and the video game, 300: March to Glory for Sony PlayStation Portable, which contains a substantial amount of new dialogue.

Wenham plays New Zealand detective Al Parker[9] alongside Elisabeth Moss in the 2013 BBC series Top of the Lake.

In 2013, Wenham returned to the stage to play the lead role of John Proctor, in the Melbourne Theatre Company's mid-year production of Arthur Miller's The Crucible.

Wenham played the role of the villain Harold Meachum in the Netflix original television series Iron Fist, which premiered in March 2017.

In 2020, it was announced that Wenham was cast as Jasper Queller in the upcoming Netflix thriller series Pieces of Her, which is adapted from the Karin Slaughter novel of the same name.

[11] In 2022, Wenham returned to work with director Baz Luhrmann again to play the role of country singer Hank Snow in the biographical film Elvis.