"I took the decision to leave my post," Garibashvili, head of the Georgian Dream coalition, said in a televised address to the nation, without disclosing the reason.
"All posts are temporary. Only God and the motherland are eternal," a stone-faced Garibashvili added.
Opposition politicians said earlier that his resignation may likely be part of the coalition's efforts to reverse a rapid loss of popularity amid economic turmoil before parliamentary elections set to take place in October 2016.
He was a political unknown before his billionaire tycoon predecessor Bidzina Ivanishvili named him interior minister in October 2012.
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Garibashvili said Ivanishvili's resignation in 2013 "had set an example for stepping down in a timely fashion".
Media reports tipped deputy prime minister and foreign minister Giorgi Kvirikashvili to replace him.
Paris-educated Garibashvili has spent almost his entire decade-long working life in the employ of the enigmatic Ivanishvili who calls him his "beloved boy."
Georgian Dream's approval ratings stood at just 18 percent last month, according to an opinion poll by the US-based National Democratic Institute.
Ivanishvili stepped down in November 2013 to make way for Garibashvili, but was widely believed to be still calling the shots.
Georgian Dream wrested power from reformist ex-president Mikheil Saakashvili's party in the October 2012 parliamentary election.