Manapul is known for his work on Witchblade and The Necromancer for Top Cow, working on the former for three years, off and on, returning for the tenth anniversary issue in 2005.
He provided covers for various titles, most notably for some G.I. Joe comics from Devil's Due Publishing.
In 2007, he signed an exclusive contract to work with DC Comics.
He also served as a guest judge in the fourth week round of Comic Book Idol, third season, sponsored by the Comic Book Resources.
In 2008 Francis became the artist for DC's Legion of Superheroes with Jim Shooter as the writer. Francis co-created the character Gazelle with Shooter before leaving the title.
In 2009, he was named to be the artist in DC's new Flash series written by Geoff Johns which stars [Flash (Barry Allen)|[Barry Allen]] in the lead role.
He was also one of the TV presenters on Beast Legends from Yap films, which currently airs Wednesday nights at 10pm EST on History Television Canada. Its premiere in the US was on September 9, Thursday at 10pm EST on SyFy.
In May 2011, DC Comics announced a massive revamp and relaunch of their entire superhero line, as part of this Francis was named writer/artist on the Flash, with his longtime colorist/collaborator, Brian Buccellato co-writing with him.
Manapul was awarded the Joe Shuster Award for Outstanding Artist in 2011.