The school, which specializes in online learning, says Frits Pannekoek will not complete his second term in office.
The university does not say why he is leaving early after eight years at the job.
A university spokeswoman says Pannekoek will remain as president until his successor is chosen by next May.
The announcement comes after a number of vice-presidents left the university earlier this year.
In a letter to staff, the chairman of the school's board of directors says the large number of changes to the executive administration will pose a significant challenge to operations.
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