Speaking on behalf of the full court less than 24 hours before the Australian Open gets underway, Chief Justice James Allsop handed down orders that will see Djokovic on a flight back home.
"This is not an appeal against the decision of the executive government," Allsop told the court. "It is an application to the court as a separate arm of government being the Commonwealth judicial branch to review a decision by a member of executive, the minister, for the lawfulness or legality of the decision on the three grounds put forward.
"These grounds focus on whether decision was, for different reasons, irrational or legally unreasonable. It is no part or function of the court to decide upon the merit or wisdom of the decision."
The decision was unanimous and full reasons will be published at a later date. Djokovic was ordered to pay costs.
Justice Allsop said he does not believe any further orders are necessary.
Djokovic was scheduled to get his Australian Open campaign underway at Rod Laver Arena on Monday evening, but Tennis Australia will need to come up with an alternative play schedule for day one.
According to ATP, world No. 150 Salvatore Caruso is expected to replace Djokovic in the men's singles draw.
It also means the 2022 Australian Open will be the first time Spanish phenom Rafael Nadal is the only member of the "Big Three" in a grand slam draw.
Djokovic released a statement soon after the verdict was handed down, claiming he was "extremely disappointed" with the outcome.
"I'd like to make a brief statement to address the outcomes of today's Court hearing," he said. "I will now be taking some time to rest and to recuperate, before making any further comments beyond this.
"I am extremely disappointed with the ruling to dismiss my application for judicial review of the decision to cancel my visa, which means I cannot stay in Australia and participate in the Australian Open. I respect the Court's ruling and I'll co-operate with the relevant authorities in relation to my departure from Aus.
"I am uncomfortable that the focus of the past weeks has been on me and I hope that we can all now focus on the game and tournament I love. I would like to wish the players, tournament officials, staff, volunteers and fans all the best for the tournament.
"Finally, I would like to thank my family, friends, team, supporters, fans and my fellow Serbians for your continued support. You have all been a great source of strength to me."
ATP also released a statement: "Today's decision to uphold Novak Djokovic's Australian visa cancellation marks the end of a deeply regrettable series of events.
"Ultimately, decisions of legal authorities regarding matters of public health must be respected. More time is required to take stock of the facts and to take the learnings from this situation.
"Irrespective of how this point has been reached, Novak is one of our sport's greatest champions and his absence from the Australian Open is a loss for the game.
"We know how turbulent the recent days have been for Novak and how much he wanted to defend his title in Melbourne. We wish him well and look forward to seeing him back on court soon.
"ATP continues to strongly recommend vaccination to all players."
