The billionaire benefactors parted ways in 2021 after 27 years of marriage but had pledged to continue their philanthropic work together. Their final divorce order filed in a Seattle court had no details on an agreement reached between the two on how to divide their marital assets.
"Under the terms of my agreement with Bill, in leaving the foundation, I will have an additional $US12.5 billion ($A18.9 billion) to commit to my work on behalf of women and families," Melinda Gates said on social media platform X, without disclosing more details about her plans.
With her departure as co-chair, the foundation will change its name to Gates Foundation and Bill Gates will be its sole chairperson, said CEO Mark Suzman.
"After a difficult few years watching women's rights rolled back in the US and around the world, she wants to use this next chapter to focus specifically on altering that trajectory," Suzman said.
The foundation is one of the most powerful and influential forces in global public health, having spent more than $US75 billion ($A114 billion) since its inception to bring a business approach to combating poverty and disease.
From 1994 through 2018, Bill and Melinda gifted about $US59.5 billion ($A90.1 billion) to the Seattle-based foundation, its website said.
Her last day at the foundation will be June 7.
"I am sorry to see Melinda leave, but I am sure she will have a huge impact in her future philanthropic work," Microsoft co-founder Bill Gates said in a post on X.
Melinda Gates, who has a net worth of $US11.3 billion ($A17.1 billion) according to Forbes, manages some of her investments and charitable work through her Pivotal Ventures. The investment company, founded in 2015, focuses on women and families.
