Sting, Robbie Williams and Emeli Sande are among the acts who will be performing in front of the Prince of Wales and the Duchess of Cornwall.
The show takes place at the Eventim Apollo in Hammersmith on 6 December and will be broadcast on ITV.
Walliams said he was "very honoured and excited" to be hosting the show for a second time.
"I was lucky enough to host back in 2012 so will be looking forward to another fabulous evening with huge talent."
This year's line up includes Funny Girl actress Sheridan Smith, Barry Gibb, One Republic, DNCE and Gary Barlow.
There will be performances from Barlow's musical The Girls, An American In Paris and Dreamgirls, as well as the cast of Cirque Du Soleil's The Beatles Love show.
Also performing on the night will be this year's Britain's Got Talent winner, magician Lance Corporal Richard Jones, and dance troupe Diversity, who previously won the show.
McFly singer Tom Fletcher will read from his book The Christmasaurus and comedians Joe Lycett, Alan Davies and Rob Beckett are also on the line-up.
The show is staged annually in aid of the Royal Variety Charity, which helps people from the world of entertainment in need of care and assistance.
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David Walliams has been announced as the host of this year's Royal Variety Performance.