Rapid antigen tests picked up the six cases on Tuesday morning and subsequent PCR tests confirmed the results.
In addition, Melbourne Victory's FFA Cup round of 16 trip to face Gold Coast Knights was postponed -- after Victory players were potentially exposed to coronavirus in Saturday's Melbourne derby against City.
"The A-Leagues can confirm that six players from Melbourne City FC's A-League Men's football department have tested positive for COVID-19 and are currently in isolation and all report to be currently feeling well," the A-Leagues said in a statement.
"The case involves double-vaccinated individuals who tested positive to a PCR test on 21 December enacted after their daily rapid tests earlier in the day.
"As a result of the number of cases, the A-Leagues have determined that Melbourne City's scheduled round six away match against Brisbane Roar has been postponed.
"The club's primary concern is for the health and safety of all players, staff and their families. All positive cases and those close to them are adhering to relevant state government health directives."
Victory had been unwilling to risk going to the Gold Coast for their now-postponed game and potentially facing Christmas in hotel quarantine.
All their players and staff have tested negative since the derby, as negative tests pre-travel had been a requirement ahead of their planned cross-border trip.
On Wednesday afternoon, the Jets confirmed Boxing Day's game against Western Sydney at McDonald Jones Stadium would be held behind closed doors with no fans or media, bar select photographers, permitted to attend.
The decision comes amid an ongoing outbreak in Newcastle and the Hunter.
"We know that many families and organisations in our community have already been affected by this recent outbreak, as have the Jets, and it is clear that we need to consider the appropriateness of staging a mass event at this time in the Newcastle region outbreak," Jets executive chairman Shane Mattiske said.
"In consultation with the APL, it has confirmed that the game should move to be played behind closed doors."
Meanwhile, the majority of Perth Glory's travelling party will be home for Christmas.
The Glory have been permitted to take a charter flight from Brisbane to Perth on Thursday and complete their remaining seven days' quarantine in managed isolation.
Perth have been in hotel quarantine since Dec. 16 after a COVID-19 case among their players had resulted in the club's entire travelling party being considered close contacts.
The player who tested positive is required to remain in Brisbane to complete his 14-day isolation period in hard quarantine.
Elsewhere, the BBL has confirmed Perth Scorchers will play their home matches scheduled for Jan. 5 and 6 at Gold Coast's Metricon Stadium.
The Scorchers are playing their remaining home fixtures on the road.
Fremantle's AFLW round two clash with GWS on Jan. 16 has been moved from Fremantle Oval to Melbourne's Whitten Oval.