Mesure was born in Somerset, England. When he 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.

In 1995, he moved to New Zealand where he soon picked up a few acting roles. Mesure has acted in, 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 both 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.

Mesure 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). He made a guest appearance on a 2013 episode of Burn Notice, playing the head of a criminal hacking syndicate.

On 30 March 2014, he played Edwin MacKaye in the episode called “Violets” on The Mentalist. From 2014 to 2018 he guest-starred in five episodes of Once Upon a Time, as the pirate Blackbeard.