"After a great deal of thought and a lot of work on our relationship, we have made the decision to end our marriage," the 65-year-old wrote on social media.
"Over the last 27 years we have raised three incredible children and built a foundation that works all over the world to enable people to lead healthy, productive lives. We continue to share a belief in that mission and will continue to work together at the foundation, but we no longer believe we can grow together as a couple in this next phase of our lives.
"We ask for space and privacy for our family as we begin to navigate this new life."
The Gates wed on New Year's Day in 1994 in Hawaii. Now 56, Melinda in 2019 credited their longevity as a couple with splitting the unpaid housework and parenting duties.
The pair met in 1987 at a trade fair. Bill by then was well-known in computing circles as the founder of Microsoft, which had just released the first version of its Windows software that would go on to dominate the industry.
Melinda herself was no slouch when it came to computers, having just completed her bachelor's degree in computer science and economics. She went to work at Microsoft, leaving in 1996 to focus on the Gates' growing family.
In 2000 the couple started the foundation which bears their name. It's since grown to be the largest of its kind in the world, focused on reducing extreme poverty and increasing access to healthcare.
Bill was once the richest man on the planet, but has fallen behind in recent years thanks to his philanthropic efforts. The Gates' split comes two years after another tech billionaire who once held that honour, Amazon founder Jeff Bezos, split with his wife of 26 years, MacKenzie Bezos.