Named CIO in 2013, Mr DuBois had been with Microsoft since 1993 where he worked in several roles mostly focused to information technology, GeekWire reported on Saturday.
Senior Microsoft employee Kurt DelBene will replace DuBois as Chief Digital Officer (CDO).
The news came after Microsoft announced nearly 4,000 job cuts from its global sales force outside the US, apparently a move to realign its focus on the growing cloud business.
The job cuts amount to less that 10 per cent of the company's total sales force.
US-based analyst house Pacific Crest Securities said last month that Microsoft Azure Cloud platform could overtake Amazon Web Services (AWS) as revenue leader in the public cloud market this year.
Microsoft has 71,000 employees in the US and 121,000 employees around the globe.