Minister Erkan Mumcu said his leaving the cabinet was due to what he called long-standing differences with the government.
"For a long time, there were recurring differences of opinion in the cabinet. These were on a wide range of issues," the 42-year-old told a press conference in Ankara on Tuesday.
"Since it is against my personal and political ethics to stay in a post where I cannot make any contribution, I decided to resign," he added.
Mumcu is the first minister to resign from the AKP government which rode to power in the November 2002 elections.
His resignation came a day after he reportedly spoke out in a cabinet meeting against government plans to pardon thousands of students expelled from school, including those kicked out for wearing Islamic headscarves, the NTV news channel suggested.
Headscarves are regarded by the establishment as a symbolic declaration against the mainly Muslim nation's strict secular order and are banned in schools and public offices.
NTV said that Mumcu reportedly criticised Prime Minister Recep Tayyip Erdogan as "insincere" and said the government should introduce a wider education reform instead, NTV said.
Mumcu has often clashed with the government and other AKP lawmakers on account of his liberal views.
"Since it is against my personal and political ethics to stay in a post where I cannot make any contribution, I decided to resign"
Turkish Culture and Tourism Minister
He was one of the few party members to oppose a controversial bill last year to criminalise adultery, a plan which was later dropped in the face of opposition from the European Union.
Parliamentary sources suggested that Mumcu could now either seek to join the centre-right Motherland Party (ANAP) - which he was a member of before joining the AKP - or to set up a new political party.
At least 20 AKP lawmakers are believed to have sided with Mumcu, the sources said.
But when asked whether he had plans to found a new party, Mumcu dodged the question and said: "Political parties are not set up by individuals but by conditions".