Victorian Health Minister Mary-Anne Thomas, Finance Minister Danny Pearson and Water Minister Gayle Tierney on Monday announced their immediate exit from cabinet before quitting parliament in November.
Their resignations follow Natalie Hutchins leaving cabinet and announcing she will not recontest the November state election.
Labor MPs will meet on Tuesday to finalise four new entrants to cabinet as factions negotiate who will get the nod.
Premier Jacinta Allan, who has faced internal factional pressure over her leadership, will then hand out portfolios before a swearing in ceremony at Government House on Wednesday.
It is expected to be the premier's last frontbench reset before voters head to the polls as Labor eyes a historic fourth term in power.
Ms Thomas' departure creates a hole in the critical portfolio of health, which she took over at the tail end of the COVID-19 pandemic in mid-2022.
The Macedon MP said she'd recognised in recent months she might not be able to give the same level of commitment for another four-year term.
"I've only known one way of working in my life and that has been to go at it full throttle," she said.
The former Bracks-Brumby government advisor and public servant said she plans to spend more time with her family and 91-year-old mother in Wodonga, as well as attending AFL games to cheer for her beloved St Kilda.
"They need it," she quipped.
Mr Pearson, who has served in a dozen cabinet roles since 2020, became choked up while reflecting on his 12 years in parliament coming to an end.
"It's a bit like the circle of life - now it's my turn to give someone else a go," he said.
Ms Tierney said she first seriously turned her mind to retiring after a bill to legislate free TAFE passed parliament in March, also citing her interstate elderly mother as a consideration.
She has been in Victoria's upper house since 2006 and spent almost seven years as training and skills minister from 2016 to 2023.
The trio all spoke at length of the "corrosive" impact of social media on democratic institutions since entering parliament, including from anonymous trolls.
Each of the ministers had left an indelible mark on Victoria, the premier said.
"I want to thank each of the three of them for their friendship," Ms Allan said.
Luba Grigorovitch, Paul Edbrooke, Michaela Settle, Tim Richardson and Paul Hamer are among backbenchers in the frame for promotion.
Ms Grigorovitch was a friend of former Victorian CFMEU secretary John Setka, who was charged in February with sending threatening emails to a staff member from the union's administrator.
Setka attended her wedding to private equity partner Ben Gray at Sorrento on the Mornington Peninsula in 2023.
Ms Grigorovitch has said she was "quite close" with Sekta during her time as Rail, Tram and Bus Union state secretary but hadn't spoke to him in "quite a while".
"If the allegations are true, he will have his day in court," she told reporters in February.
Opposition Leader Jess Wilson said the state would continue to remain under the control of a "tired" and incompetent government that was letting Victorians down.
"To shuffle the deck chairs is going to do nothing to actually change the direction of this state," she said.
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