Matthews currently oversees more than $1bn (£621m) in marketing spend across advertising, PR, events and packaging.
Microsoft has previously said she was “instrumental” in driving growth and “building the Microsoft brand”, having been involved in the launch of products such as the Xbox.
Microsoft is reportedly seeking a replacement. Matthews is not thought to have a job to go to.
Microsoft also recently lost its business division president Stephen Elop who joined as Nokia as CEO and announced a partnership with Microsoft to make Windows Phone 7 OS its lead smartphone platform earlier this year.
The technology company has also lost several other high-profile executives including its chief software architect Ray Ozzie and its president of server and tools Bob Muglia in the last two years.