From 11.59pm on Wednesday, the pandemic declaration will lapse and Victorians won't have to isolate after testing positive for COVID-19, with people instead strongly recommended to do so.
Rapid testing of close contacts will also be strongly recommended.
On the advice of Chief Medical Officer Paul Kelly, Victoria and other jurisdictions unanimously agreed at national cabinet last week to ditch mandatory COVID-19 isolation from October 14.
But the Victorian government on Friday announced it would opt to end the requirement early rather than extend the declaration by 24 hours.
Worker COVID-19 vaccination mandates will remain in Victorian hospitals, aged care facilities, day surgery centres and the ambulance service under directions issued by the Department of Health.
Occupational health and safety laws and public service directions may also still require workers to have COVID-19 jabs, at their employer's discretion.
Premier Daniel Andrews said the new framework would give people the choice to do what is right for them and their community.
"We're making sure there are still requirements in place to protect our dedicated healthcare workers and vulnerable Victorians in high-risk settings like aged care, disability settings and hospitals," he said.
The pandemic declaration replaced Victoria's expiring state of emergency powers in December last year, after the Andrews government passed contentious pandemic-specific legislation.
Opposition health spokeswoman Georgie Crozier said the government's decision was not public health-minded but instead an election ploy, 50 days out from the Victorian poll.
"Victorians won't forget the last two and a half years under Labor," she said.
Melbourne spent 263 days under stay-at-home orders across six lockdowns from March 2020 to October 2021.
Once reaching tens of thousands of cases a day, Victoria on Friday recorded 9230 new COVID-19 infections and 43 deaths over the past seven days, with both figures down from the previous week.
The shifting landscape comes as Melbourne prepares to welcome an mRNA research and development centre after Victoria struck an agreement with a German biotech company.
BioNTech has agreed in principle with the state government to develop a clinical-scale mRNA manufacturing facility in Melbourne.
The arrangement would see BioNTech deliver mRNA therapeutics and vaccines for research and clinical trials, including infectious diseases, cancer medicines and personalised cancer treatments.
The new facility will support researchers to translate their work into medical breakthroughs and establish clinical-scale mRNA manufacturing.
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