Nadal, Federer and Murray had already been confirmed for the 2022 edition of the tournament, to be held in London in September.
Djokovic, who won his 21st grand slam title at Wimbledon earlier this month, has now joined his fellow greats to add to a formidable Team Europe line-up.
The Serb most recently competed in the Laver Cup in 2018, and while it is yet unclear if he will be able to feature at the upcoming US Open because of his COVID-19 vaccination status, Djokovic is relishing the chance to play alongside the best players of the modern era.
He said: "It's the only competition where you can play in a team environment with guys that you're normally competing against and to be joining Rafa, Roger and Andy – three of my biggest all-time rivals – it's going to be a truly unique moment in the history of our sport."
"I don't think I could have imagined having these four icons of the sport on one team together," Team Europe captain Bjorn Borg said.
"I know they, like I, appreciate the significance of this moment and will be truly up for it.
"Each year our goal is to win. With Rafa, Roger, Andy and Novak on the team, I like our chances."
The quartet has accounted for 66 of the past 76 grand slam titles won in men's tennis, while one of them held the No.1 spot every week between February 2004 and February 2022, when Daniil Medvedev ended that run.
Felix Auger-Aliassime, Taylor Fritz and Diego Schwartzman have been confirmed to be competing Team World, led by John McEnroe.
Six players will compete on each team, meaning Team Europe still has two more spots to fill, while Team World has three spare.