When Mesure was five, his family moved to Australia and he grew up in Sydney. Mesure attended Newington College (1982–1987) and graduated from the National Institute of Dramatic Art, Australia, with a degree in Performing Arts (Acting) in 1995. The same year he moved to New Zealand where he soon picked up a few acting roles. Mesure has acted, directed, designed, and written upwards of thirty productions for the Sydney University Drama Society while studying law. In 1998 he was nominated for a Best Actor New Zealand Television Award for his work as Ryan Waters on the New Zealand soap opera, City Life and in 2003 he won the Best Supporting Actor award for his work as Kees Van Damm on the New Zealand drama, Street Legal. Mesure appeared as a supporting character in Season 1 of the American TV series V, and was promoted to a regular series cast member for Season 2.
Mesure is known internationally for his role as Kyle Hobbes in the 2009 re-imagining of V and the archangel Michael in the TV series Hercules: The Legendary Journeys and Xena: Warrior Princess. He has played guest roles on hit shows such as Lost, Without a Trace, Bones and Stacked. Mesure has also had a recurring role as the reporter JD Pollack on Crossing Jordan. He has previously played movie roles in Boogeyman with Barry Watson, Emily Deschanel and Lucy Lawless, Mee Shee: The Water Giant with Bruce Greenwood, Rena Owen and Joel Tobeck, and Superfire with D. B. Sweeney, Chad Donella and Diane Farr.
In 2009, he played Detective-Sergeant Zane Gerard in the New Zealand drama Outrageous Fortune.
In 2010, he played Alec Ross, the lead character in Television New Zealand's new drama series, This Is Not My Life.
Charles Mesure has joined the final season cast of Desperate Housewives as Ben Faulkner, a ruthless self-made contractor who shares a connection with Renee Perry (Vanessa Williams).
- 1996-1998 City Life
- 1997 Mirror, Mirror II
- 1997 Duggan
- 1997-2001 Xena, la guerrière
- 1998 Tiger Country
- 1998-1999 Hercule
- 1999 The Life & Times of Te Tutu
- 1999 Les mystères de la bibliothèque
- 2000-2003 Street Legal
- 2002 Superfire: l'enfer des flammes
- 2003 Skin & Bone
- 2005 Briar & Graves
- 2005 Lost - Les disparus
- 2005 Boogeyman - La porte des cauchemars
- 2005 Stacked
- 2005 FBI - Portés disparus
- 2005 Mee-Shee: The Water Giant
- 2005-2007 Preuve à l'appui
- 2006 Cold case - affaires classées
- 2006 Bones
- 2007 Las Vegas
- 2007 Ghost Whisperer
- 2009 Outrageous Fortune
- 2010-2011 V
- 2010 This Is Not My Life
- 2010 Kaitangata Twitch
- 2011-2012 Desperate Housewives