Mr Andrews will step down as the state's leader and as the member for Mulgrave effective 5pm on Wednesday.
"Nine years ago, I visited Government House to be sworn in as the 48th premier of Victoria - it has been the honour and privilege of my life," he told reporters.
"I'm also proud to think of all that we have achieved over these nine years in good times and always working hard to do what's right, not simply what's popular."
He made the announcement during a snap press conference at state parliament on Tuesday with his wife Cath and their sons beside him.
Members of his cabinet watched on from behind journalists, including presumed successor Jacinta Allan and Treasurer Tim Pallas.
"Recently in talking to my kids and Cath, thoughts of what life will be like after this job has started to creep in," Mr Andrews said.
"I have always known that the moment that happens, it is time to go and to give this privilege, this amazing responsibility to someone else.
"It is not an easy job being premier of our state, but that is not a complaint that is just fact.
"It requires 100 per cent from you and your family, that of course is time-limited and now is the time to step away."
Mr Andrews became premier in November 2014, booting out a first-term Liberal government, and led Labor to two more victories in 2018 and 2022.
During the 2022 election campaign and in the months after, Mr Andrews repeatedly said he would stay for the full four-year term.
On Tuesday he said the change of heart was a recent decision.
"It was true then but I changed my mind," he said.
Politicians who were watching on laughed as Mr Andrews spoke of bracing for a period of adjustment when he leaves such a fast-paced job.
He gave the speech at a rooftop terrace at parliament on a sunny Melbourne day and faced questions from a larger than usual media pack including more than a dozen camera operators and photographers.
His replacement will be picked at a caucus meeting at noon on Wednesday.
Mr Andrews has spent 13 years leading the Victorian Labor Party, starting as opposition leader and was first elected to his seat of Mulgrave in 2002.
In his time as premier Victoria became the first state in the country to introduce euthanasia laws and other progressive legislation, including abortion clinic safe zones, decriminalising sex work and banning gay conversion practices.
He achieved gender equality within the ministry and set the state on the path to treaty with Indigenous Victorians.
But his time was not without controversy.
He had to sack former Labor powerbroker Adem Somyurek from the ministry twice, first for bullying and then for branch-stacking in a scandal that claimed the scalps of three other ministers.
From the time Labor was elected, it came under scrutiny for the use of parliamentary allowances for its 2014 election campaign, MPs not living in their electorates and claiming taxpayer money for it, and even chauffeuring pet dogs in ministerial cars.
Victoria also endured the harshest COVID-19 pandemic restrictions and a disastrous hotel quarantine program that led to the virus spreading despite six lockdowns.
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