Benny Gantz, who leads the Israel Resilience party, is leaving Israel's government, he announced in a televised speech according to several media outlets.
The resignation occurs in protest at how Prime Minister Benjamin Netanyahu has handled the war in Gaza.
Gantz is often considered Netanyahu's most formidable political opponent.
He has sat on Israel's decision-making war cabinet, which has only three members, since shortly after the Hamas terror attack on October 7, when the war in Gaza broke out.
When he now resigns, the cabinet consists only of Netanyahu and Defence Minister Yoav Gallant, both from the Likud party.
The general and former chief of staff Gantz has threatened to resign for several weeks if Netanyahu does not approve a post-war plan by June 8.
Gantz had, among other things, demanded that all hostages be brought home, as well as the creation of an international administration for a demilitarized Gaza after the war.
On Saturday, when the deadline expired, Gantz was due to hold a press conference, where he would likely announce his resignation. However, the news that Israel's military had freed four hostages caused him to postpone the statement.
Netanyahu's government is caught between centre forces like Gantz and extreme right-wing parties, which also have ministerial posts and have set their own ultimatums to avoid bringing down the government.
Gantz's resignation is unlikely to topple the coalition government, as a majority in parliament still backs Netanyahu. However, it is believed to make the prime minister increasingly dependent on allies on the right-wing flank.
The right-wing security minister Itamar Ben-Gvir writes on social media that he now demands a place in the war cabinet. Israeli media, however, reports that Netanyahu is instead considering disbanding the cabinet.
In his speech, Benny Gantz says Netanyahu has made it impossible to achieve a total victory in Gaza, and that the government should prioritise bringing home the hostages over political survival.
Benjamin Netanyahu asks Gantz to stay.
"Benny, it's not time to give up the fight – it's time to unite our forces", writes the prime minister on X.