The Adelaide and Port Adelaide AFL sides will relocate to Victoria, meaning all 18 AFL clubs will be temporarily based in the state.
The two South Australia clubs will fly out for Melbourne on Wednesday afternoon due to an increasingly complicated COVID-19 situation across Australia.
Despite the SA government deciding against a lockdown - after the state recorded five new COVID-19 cases on Wednesday without any community transmission - the AFL has opted to move the Crows and the Power squads.
Port's clash with Hawthorn at Marvel Stadium on Saturday will go ahead as planned, but a new venue will need to be found for Adelaide's game, previously scheduled for the Adelaide Oval, against the Brisbane Lions.
The game may take place out of Melbourne but remain in Victoria, with Mars Stadium in Ballarat being seriously considered as a possible venue.
AFL broadcasting and clubs manager, Travis Auld, said:
"Bringing the two South Australian teams to Victoria today minimises risk for the competition as we progress the season in a constantly changing environment.
"As of this evening we will have all 18 teams in Victoria and, as a competition, we will continue to remain adaptable where required.
"The two teams travelling today will fly to Victoria via a charter flight and will remain in the state ahead of this round's matches."
Sixteen of the league's 18 clubs are already in Victoria after Brisbane, Gold Coast, West Coast and Fremantle arrived in Melbourne on Tuesday night due to lockdowns in south-east Queensland and Perth.
The South Australian sides' imminent arrival comes as the AFL scrambles to finalise its fixture just a day out from the opening match of round 16.
The Gold Coast Suns' Thursday night home clash with Richmond has already been moved from Metricon Stadium to Marvel Stadium.
The Tasmanian government has denied the AFL's application to host the Fremantle-Carlton match in Launceston, meaning Geelong's GMHBA Stadium will host the round-16 game.
The Dockers pushed for the match to be held in completely neutral territory considering it was originally their scheduled home fixture in Perth.
Tasmania Premier, Peter Gutwein, said:
"As a result of the current national risk the game will not go ahead in Tasmania.
"I know that will disappoint many people, especially Carlton supporters who I'm sure there are many of in the state."
It is a contrasting situation to the same time last year when Melbourne's second wave of COVID-19 forced all Victorian clubs to relocate north and the grand final was played in Brisbane for the first time.
Sydney and GWS are already based in Melbourne, having flown out last week because of Bondi's growing COVID-19 cluster.
The Swans' home game against West Coast at the SCG has been shifted to GMHBA Stadium on Sunday, while the Giants will play at the MCG for the second-straight week when they face Melbourne on Saturday.