The motion to sack Reza Faraji-Dana, whose responsibilities included the country's universities, was backed by 145 of the 270 lawmakers present.Conservatives had been angered by his decision to let students expelled from university after the anti-government unrest in 2009 return to campus.
Mr Rouhani had urged parliament to have greater confidence in the minister.
Mr Faraji-Dana was also accused of nominating for senior department positions people who were involved in the mass opposition protests that followed the disputed re-election of President Mahmoud Ahmadinejad in 2009, which the authorities considered a "plot".
Critics said he had tolerated student publications that questioned Islamic teachings and promoted sedition and riots.
President Rouhani was elected last year on promises of greater openness and diplomatic engagement with the West.
In a speech on state TV, he praised the work of Mr Faraji-Dana, whom he described as a "polite and knowledgeable minister", but said he would comply with the result of Wednesday's vote to preserve national unity.
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