Bill and Melinda Gates announced in identical tweets Monday that they were ending their 27-year marriage.
They said they "no longer believe" that they can grow as a couple.
The American business magnate and co-founder of Microsoft is the third-richest man in the world.
The couple met during a business dinner in 1987, when Melinda Gates was a product manager at Microsoft. The pair then married around seven years later.
The financial details of the separation have not been revealed. Both Gateses have signed on to Warren Buffett's Giving Pledge, promising to donate most of their fortune to charitable causes.
What did the Gateses say?
"After a great deal of thought and a lot of work on our relationship, we have made the decision to end our marriage," Gates tweeted.
"We have raised three incredible children and built a foundation that works all over the world to enable all people to lead healthy, productive lives,'' they said.
"We ask for space and privacy for our family as we begin to navigate this new life.''