Twickenham has hosted the Premiership's double-header since 2004
Wasps have signed a three-year deal to host a game at Twickenham in celebration of St George's Day.
The first game will take place on 24 April next year, a day after St George's Day, and will be against Bath in the Premiership.
"This move is about finding that perfect venue for the celebration of St George's Day," said owner Steve Hayes.
Harlequins signed a three-year deal last year for Twickenham to host a Christmas fixture.
The first of those games, against Leicester in 2008, was watched by a restricted crowd of 50,000 although Quins hope to have an 82,000 sell-out for this year's match against Wasps on 27 December.
Twickenham has also hosted the domestic season's opening double-header since 2004.
As well as the games at Twickenham, Premiership leaders Saracens played Northampton at Wembley in September and will hold two more matches at the venue this season.
However, Hayes insists he does not intend to hold more than the St George's Day game at the home of English rugby.
"It is important that our supporters know that it is not our ambition to follow the trend of moving game after game to bigger venues," he said.
"Adams Park is our home and given our record to date I know that our fans and players enjoy the matchday here.
"This is a special occasion and I want our supporters to enjoy that variety and excitement."
He added: "Sport for me shows passion in identity, especially our national identity, and therefore I am delighted that London Wasps will take hold of and develop this St George's Day fixture."
Wasps say they will donate £1 per ticket to the Help for Heroes charity, which works to improve treatment and facilities for injured members of the armed forces.