The 2020 Super League Grand Final will be played at Hull FC's KCOM Stadium on Friday, 27 November, the first time the event will not be held at Old Trafford.
The decision to move the venue comes after the season was pushed back because of the coronavirus pandemic.
Manchester United's Old Trafford has hosted since 1998 but is unavailable because of fixture congestion.
Usually taking place on a Saturday, it is the first time the event will go ahead on a Friday evening (20:00 GMT).
"It's unfortunate that the Covid-affected fixture schedules, of both Manchester United and Super League, mean that despite our best efforts we have had to find an alternative to the only home the Super League Grand Final has ever known," explained Super League executive chairman Robert Elstone.
"We will miss Old Trafford. Most of all we all will miss the nerve-jangling atmosphere created by 70,000 fans.
"We are excited about the new kick-off time. Friday nights have always featured strongly in the rugby league calendar."
Old Trafford has been ruled out as United host Champions League fixtures on Tuesday, 24 November and Wednesday, 2 December.
Last season, St Helens beat Salford Red Devils 23-6 in the 2019 Grand Final in front of 64,000 spectators at Old Trafford.