As a nine-time Mosconi Cup winner, Strickland is regarded as one of the greatest players in history of the sport.
His return for the 2021 event came as a major shock considering the former world champion has recently turned 60.
However, as revealed by the event's managing director Emily Frazer, Strickland will not compete and will be replaced by the captain of Team USA, Jeremy Jones.
Frazer said: "At this moment in time, we're operating in difficult circumstances with our current climate. It's our priority to follow government guidance for the safety of everyone at our event.
"Unfortunately, due to a possible Covid exposure, Earl Strickland has withdrawn from the event.
"But, five-time Mosconi Cup winner, former US Open champion, Jeremy Jones is coming out of retirement."
"Both teams are devastated, we feel for Earl who is very healthy and is now isolating."
The news comes as a major blow not only for Team USA but also for the event which was largely billed around Strickland's return.
Following the announcement, America have tumbled down the betting market and are currently priced at 5/1 to regain the Mosconi Cup.
Speaking about the situation, Jones said: "He deserves to be here. It wasn't long that I messaged the team. It's the guidelines and safety is first.
"This may be the most unfortunate circumstance. I'm going to stand tall like every American would and try and represent Earl and a lot of others who can't be here and everyone back home."
Vice-captain of Team USA, Shane Van Boening, added: "I was talking to Earl nearly every day. He called me nearly every day saying that he was practicing, working, doing thousand sit ups. He was working hard and it's an unfortunate situation."
The Mosconi Cup begins on Tuesday, December 7, from the Alexandra Palace in London.