Sinofsky, 47, who joined Microsoft as a software design engineer in 1989, departed the company on Tuesday weeks after it unveiled its Windows 8 operating system and Surface tablet.
His departure also comes just days after Microsoft CEO Steve Ballmer admitted to French newspaper Le Parisien that sales of its Surface tablet had started "modestly".
“It is impossible to count the blessings I have received over my years at Microsoft," Sinofsky said in a statement. "I am humbled by the professionalism and generosity of everyone I have had the good fortune to work with at this awesome company."
According to a report by news agency Reuters, an unnamed executive at the company said the decision was "mutual" and did not believe that Sinofsky, who was expected by some to succeed Ballmer as CEO at Microsoft, would be taking a job at another company in the near future.
While Microsoft did not give a reason for Sinofsky’s departure, it confirmed that Julie Larson-Green, who was previously responsible for programme management, user interface design and user experiences for Microsoft Office and early versions of Internet Explorer, will be promoted to lead all Windows software and hardware engineering.
Tami Reller, Microsoft’s chief financial officer and chief marketing officer, will assume responsibility for the business of Windows, Microsoft said.
In a statement, Steve Ballmer praised Sinofsky for his contribution to the company: “I am grateful for the many years of work that Steven has contributed to the company. The products and services we have delivered to the market in the past few months mark the launch of a new era at Microsoft.
"We’ve built an incredible foundation, with new releases of Microsoft Office, Windows 8, Windows Phone 8, Microsoft Surface, Windows Server 2012 and ‘Halo 4’, and great integration of services such as Bing, Skype and Xbox across all our products," said Ballmer, adding that it was "imperative that we continue to drive alignment across all Microsoft teams, and more integrated and rapid development cycles for our offerings".