Sinofsky's departure comes just weeks after the Redmond, Wash., software company launched Windows 8, which represented a major overhaul of its ubiquitous computer operating system.
Company veteran Julie Larson-Green has been promoted to lead all Windows software and hardware engineering, Microsoft said. Tami Reller will take over responsibility for the Windows business while retaining her posts as chief financial officer and chief marketing officer.
The company did not say why Sinofsky is leaving.
In a statement, Microsoft CEO Steve Ballmer expressed gratitude for Sinofsky's contribution to the company. He indicated the need for the company to further integrate its array of offerings, which in addition to Windows includes services such as Bing, Skype and Xbox and a new tablet computer, as it begins what he called "a new era at Microsoft."
Ballmer said "it is imperative that we continue to drive alignment across all Microsoft teams, and have more integrated and rapid development cycles for our offerings."
The launch of Windows 8 last month heralded the biggest change to the industry's dominant operating system in at least 17 years. It attempts to bridge the gap between personal computers and fast-growing tablets with its touch-enabled interface.
Larson-Green has been with Microsoft since 1993. She was responsible for program management, user interface design and research, as well as development of all international releases for Windows 7 and Windows 8, Microsoft said.
In her new role, she will be responsible for all future Windows product development in addition to future hardware projects.