Panos Kammenos, whose Independent Greeks party props up the government of Prime Minister Alexis Tsipras, has long opposed the accord with neighbouring Macedonia signed by their governments last year.
Greece's right-wing defence minister Panos Kammenos resigned on Sunday in protest at a deal ending a long running dispute with Macedonia over its name, clouding the future of the coalition government months before national elections.
"The Macedonia name issue... doesn't allow me not to sacrifice the minister's chair," Kammenos said after meeting Tsipras on Sunday morning. He said he would also pull six other ministers from his party out of the government.
The impact of the resignation on the governing coalition was not immediately clear. Parliamentary elections are due in Greece by October. Tsipras's coalition has 153 seats in the 300-strong parliament, 145 of them from his leftist Syriza party.
Kammenos, who forged a coalition pact with Tsipras in 2015, never concealed his hostility to the deal with Skopje, which renames the tiny Balkan country Republic of North Macedonia.
Greece has a province called Macedonia and long demanded Skopje change its country name to remove what Athens considered to be an implied claim to Greek sovereign territory.
Macedonia's aspirations to European Union and NATO ties had been blocked by Greece over the name dispute.
Kammenos has called the accord a national sell-out and had repeatedly threatened to leave if it came before the Greek parliament for ratification — expected later this month.
Kammenos said any deal including "Macedonia" in the name of the Balkan state to Greece's north was unacceptable as the name was irrevocably tied to Greek civilisation and culture.
The main opposition, conservative New Democracy party, which is leading pre-election polls, has said it will block the deal. The government hopes, however, that the pact will still pass with the support of centre-left and independent lawmakers.
Macedonia's parliament ratified the deal by passing an amendment to the constitution on Friday.
The two countries struck the deal on the new name in June last year, but Macedonia will start using it only after the parliament in Athens also approves the change.
A dispute over the matter triggered the resignation of Greece's foreign minister, Nikos Kotzias, in October. Kotzias was an architect of the accord but left because he feel insufficiently supported by Tsipras in clashes with Kammenos.