In an email on Monday, Ambulance Victoria staff were informed chief executive Tony Walker would resign from his post in December after eight years in the role.
Professor Walker revealed he was battling bowel cancer earlier this year and took leave to undergo chemotherapy.
He is in remission but said the diagnosis and treatment have changed his perspective on life.
"I'm 60 next year. I'm not going to hang the boots up. I still hope to contribute to public life in some way," Prof Walker told Melbourne radio station 3AW on Monday.
"But it is about trying to balance. This is an all-consuming job."
Prof Walker denied he was pressured to resign after the service was beset by issues during the COVID-19 pandemic, including ramping and "code red" emergencies linked to surging demand.
He said ambulance response times were still not good enough.
"They've stabilised which I'm very pleased about but we've got a way to go," he said.
Ambulance Victoria's cultural failings were laid bare in March in the second part of a wide-ranging review by the Victorian Equal Opportunity and Human Rights Commission.
The final report found white, able-bodied men were favoured for promotions, limiting opportunities for others.
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