Eschbach, recruited by Office chief Jeff Raikes from Adobe Systems a year ago to help spur the expansion of Microsoft Office, plans to leave Dec. 1.
In a statement, Microsoft credited Eschbach for his role in last month's launch of Office 2003.
"Joe played a critical role in overseeing the launch of Office 2003," the company said. "We are sad to see him leave."
Microsoft said Eschbach, a corporate vice president, will be replaced by Chris Capossela, a 12-year Microsoft veteran and head of the company's Project unit.
Eschbach's hiring had fueled speculation that Microsoft was trying to develop a "PDF killer."
His departure--to pursue "new opportunities," according to a company representative--comes shortly after mobile phone unit executive Juha Christensen said he would leave Microsoft to start his own company.
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