Health minister Jaala Pulford is the latest in a string of Victorian government ministers to announce she will not contest the state election.
The member for the Western Victoria region said her many years in office had been rewarding.
"Around the time of the 2006 Commonwealth Games my family was driving through Melbourne," Ms Pulford said in a statement.
"My husband Jeff pointed out a big building and said: 'hey kids, mum is going to work there'.
"Four-year-old Sinead exclaimed to her little brother, 'It's a fairy castle!'.
"That little brother is now 18. We still call Parliament House 'fairy castle' and, while that may never change, the time has come for me to seek new challenges."
Ms Pulford was conscious she was making the decision to step aside on the eve of November's state election, but said she was absolutely confident that the time was right for her and the Labor government.
"I've given my all to public life, but it's given me so much more," she said.
"It's time for me to make way for the next generation, and I cannot wait to see them thrive."
Ms Pulford was elected in 2006 and holds Victoria's employment, small business, resources, innovation, medical research and the digital economy portfolios.
Premier Daniel Andrews said Ms Pulford would remain in her portfolios until the end of the term, continuing to support flood-recovery efforts until a new government was formed.
"For as long as I've known her, Jaala has been a devoted advocate for working people, making their conditions better and fairer, speaking up for them in the face of gross injustices," he said
Labor underwent a major cabinet reshuffle in June after a mass exodus of ministers.
Former deputy premier James Merlino, health minister Martin Foley, trade minister Martin Pakula, and police minister Lisa Neville are among those who revealed they would not recontest their seats in November and immediately stepped down from cabinet.
Other Victorian government ministers to bow out this term include Gavin Jennings, Marlene Kairouz, Robin Scott, Jenny Mikakos, Jill Hennessy, and Luke Donnellan.
Mr Andrews recalled Ms Pulford's inaugural speech at Victoria's Legislative Council touched on the profound role decent work could play in giving people dignity and the duty government had to protect workers.
"She carried that compassion with her into parliament and I have no doubt it's what has driven her every day," Mr Andrews said.
Ms Pulford's daughter Sinead died of cancer, aged 13, shortly after Labor came to government in 2014.
Mr Andrews said the minister's colleagues were, and still are, in awe of her strength.
"To see her continue to manage her ministerial responsibilities with such heart, while holding on to that pain, was nothing short of remarkable," the premier said.
"She made the Victorian parliament a kinder, more thoughtful place."
Health Minister Mary-Anne Thomas described Ms Pulford as a fantastic minister who has been through a lot.
Ms Thomas said despite the loss she was confident in the party's cabinet.
