The BBC has confirmed the show has ended after 12 episodes, with Walliams now moving on to work on other projects instead; including his own sketch show.
The comedy star revealed the news via Twitter, posting: "Excited to say I'm making a new sketch show for @BBCOne The BBC asked for another #BigSchool series but sadly there wasn't time to do both."
This news comes 12 years after Walliams and Matt Lucas found fame via the TV version of Little Britain. This new project will be Walliams first sketch series since Come Fly With Me, the airport-based series he launched with Lucas in 2010.
BBC Comedy executive Shane Allen has been commissioning more sketch show projects across the last year to make up for current lack of shows of that genre across the BBC's TV network. The Javone Prince Show starts this weekend, whilst other projects in development include The Tracey Ullman Show.
Talking about the end of Big School, a BBC spokesperson said: "Writing and filming a series like Big School takes up a huge amount of time and with David's schedule being absolutely jam-packed, after two successful series the show won't be coming back to BBC One. We are working on several new projects with David."
Walliams is due to appear on BBC One later this month in the new Agatha Christie drama series Partners In Crime (Trailer). He is also thought to be working with the BBC to make further one-off Christmas specials based on his hit series of children's books.
It was reported last month that Walliams, who is a judge on Britain's Got Talent, is also currently developing the idea for a sitcom set around a TV talent show.
Big School, which was written by Walliams alongside The Dawson Bros, launched in August 2013. The show started with over 4 million viewers, however the second series achieved an average of under 3 million.
The sitcom focused on the rivalry between science teacher Mr Church (Walliams) and PE teacher Mr Gunn (Glenister) to impress French teacher Miss Postern (Tate). It also featured the actors Frances de la Tour, Joanna Scanlan, Steve Speirs, Daniel Rigby, James Greene and Jocelyn Jee Esien.
Further details on Walliams' new sketch show are expected to be revealed later in the year.