His departure comes just weeks after Microsoft launched Windows 8, the latest edition of its flagship product, seen as key to the firm's future.
Microsoft did not give any reason for Mr Sinofsky's departure.
The company said Julie Larson-Green will be promoted to lead all Windows software and hardware engineering.
"The products and services we have delivered to the market in the past few months mark the launch of a new era at Microsoft," Steve Ballmer, chief executive of Microsoft said in a statement.
"To continue this success it is imperative that we continue to drive alignment across all Microsoft teams, and have more integrated and rapid development cycles for our offerings."
This post has been edited by ganbu: 12 November 2012 - 10:47 PM