Jeff Raikes heads the division that includes Microsoft Office and Exchange Server, and which brings in more than $16bn in yearly revenues.
Raikes joined the company in 1981. His credits include stints as director of applications marketing and vice president of Office systems.
Microsoft plans to divide Raikes's duties into two positions. Former Juniper Networks chief operating officer Stephen Elop will take over as president of Microsoft Business Division.
Elop will oversee the Information Worker, Microsoft Business Solutions and Unified Communications branches.
The Server and Tools Business will become a separate operation run by Bob Muglia, who will report directly to chief executive Steve Ballmer.
"There is no overstating the incredible impact Jeff has had during his amazing career at Microsoft," said Ballmer.
"Leading our business division, Jeff and his team have delivered terrific results while reshaping and expanding the portfolio of our business-related products and services to ensure a very healthy future for our customers, partners and Microsoft."
However, Raikes's departure is likely to be overshadowed by another high-profile retirement at Microsoft.
Founder and chairman Bill Gates will be stepping down from the company in June to concentrate on his charitable foundation.
Microsoft business chief to step down
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