Manford started his comedy career by winning the North West comedian of the year title in 1999. A year later, he won the Leicester Mercury comedian of the year, and was a finalist in the So You Think You're Funny? new act competition.

He made his Edinburgh Fringe debut in 2005 with Urban Legend, a show that was nominated for the main Perrier award. The following year he won the Chortle award for best breakthrough act.

He embarked on his first solo tour of the UK in September 2008, a month after hosting the topical Channel 4 show Tonightly

He became increasingly well-known thanks to his role on the Channel 4 panel show 8 Out of 10 Cats, and in 2010 hosted the high-profile Comedy Rocks for ITV. In May 2010 he was confirmed as the new co-host of BBC One's The One Show.