Saracens have agreed a five-year deal to play their annual showpiece match at Tottenham Hotspur's new stadium.
Spurs will play their first game at the 62,062-capacity ground against Crystal Palace on Wednesday (19:45 BST).
Sarries have staged selected home games at Wembley Stadium and London Stadium over the past decade.
"It's a special opportunity to partner with our fellow north Londoners, with whom we share so many core values," said Sarries chairman Nigel Wray.
"Tottenham Hotspur have shown themselves to be true innovators in the development of their new stadium.
"They are, like us, a club who care massively about their community; who strive to create opportunities in their local area, and who have had such an impact on the young people they work with."
Four-time Premiership champions Saracens first played their annual showpiece game at Wembley in 2009, but have hosted it at London Stadium for the past two years.
Built on the site of their old White Hart Lane ground, Tottenham's new stadium has cost £1bn and taken almost two years to construct.
It has hosted two warm-up events; an Under-18 match between Tottenham and Southampton and a legends game between Spurs and Inter Milan.
Two NFL matches will be played at the stadium later this year, and Tottenham chairman Daniel Levy said the agreement with Saracens reinforces their aim to "deliver a world-class multi-use venue".
"To attract one of world rugby's biggest club sides will bring a new audience to the area, as well as help drive significant socio-economic benefits for businesses and local people," Levy added.
"This is an exciting partnership and, alongside Premier League and NFL matches, it is one that continues to underline our desire to create a sports and entertainment destination that we believe can transform this area of London."