Israel on Thursday said it had killed Hamas’s leader, Yahya Sinwar, in Gaza.

The country’s foreign minister confirmed that Sinwar was killed. Sinwar, a U.S.-designated terrorist, triggered a war with Israel in Gaza in October 2023 that has since expanded to a multifront conflict in the Middle East. His death marks the severest blow yet to Hamas in more than a year of war.

The killing of Israel’s most wanted militant is also a major win for Prime Minister Benjamin Netanyahu, who vowed to destroy Hamas’s leadership and military capabilities in the Gaza Strip.

Hamas didn’t immediately respond to a request for comment.

Sinwar, who has been Hamas’s top leader in Gaza for years, took control of the group’s political bureau in August after Israel killed the previous leader, Ismail Haniyeh, the preceding month.

Sinwar was widely viewed as the architect of the Oct. 7 attacks that killed 1,200 people in southern Israel and led to the kidnapping of around 250 others.

Around 100 hostages remain in captivity in Gaza, including many dead. Talks between Israel and Hamas to secure the release of the remaining hostages have collapsed in recent months, largely due to the intransigence of Sinwar and Netanyahu.

The Israeli military said there was no presence of hostages in the area of operations in Gaza. Israeli officials had previously said they believed Sinwar surrounded himself with hostages as a security measure.

The conflict sparked by the Oct. 7 attacks has killed more than 42,000 people in Gaza, most of them civilians, according to Palestinian health authorities. The figures don’t tally the number of combatants killed.

During the war, Israel has killed the head of Hamas’s armed wing, Mohammed Deif; his deputy Marwan Issa; and a string of lower-level commanders.

Earlier this month, the Israeli military also said it killed Rawhi Mushtaha, another senior Hamas political official and one of a few people considered closest to Sinwar. The two set up Hamas’s internal police force in the 1980s, spent time in prison together and were both released in a prisoner swap in 2011.

For years, Hamas had been split between hard-liners such as Sinwar, who view the deaths of civilians as necessary to destabilize Israel, and militants who countenance violence but want the group to preserve some political legitimacy as a route to achieving its aims of a Palestinian state.

After Sinwar became leader in August, he began imposing a more violent vision of Hamas on the group, The Wall Street Journal reported.

“Our enemies cannot hide. We will pursue and eliminate them,” Israeli Defense Minister Yoav Gallant said on X on Thursday.

Top Biden administration officials immediately scrambled to confirm the initial reports that Sinwar had been killed, with top White House aides contacting their Israeli counterparts to see if there were any developments. The U.S., which has already called on Israel to wind down operations in Gaza, may use this moment to further pressure its ally to end the fighting.

As the news broke, President Biden was making his way to Germany to meet with European counterparts to discuss the war in Ukraine. Top Pentagon officials and commanders learned about Sinwar’s possible death as aides interrupted their morning meetings and shared news reports of the strike, defense officials said.

Sinwar began actively planning an attack in 2021, negotiating with Iran over funding for a large-scale assault that the Hamas leader said would lead to Israel’s destruction within two years, according to documents the Israeli military said they retrieved from Gaza and shared this month with the Journal.

The brutality of the attacks on Oct. 7, 2023, and the atrocities committed by Hamas and other Palestinian groups shocked the international community, causing even some members of Hamas to criticize Sinwar.

Alongside Hamas’s military leaders, Israel also has since killed Haniyeh, the former head of its political leadership, and his deputy, Saleh al-Arouri, who died in an Israeli airstrike on a building in Beirut in January.

Sinwar could be succeeded by his deputy in Gaza, Khalil al-Hayya, who has represented Hamas in cease-fire negotiations with Israel, or by former Hamas leader, Khaled Meshaal. Sinwar’s ascension to leader of Hamas in August cemented the group’s ties with Iran and his death could signal another shift in strategy.

Over the course of a year, Israel’s military has systematically moved from north to south along the Gaza Strip, dismantling Hamas’s armed wing, Izz ad-Din al-Qassam Brigades. Even so, the Israeli military has struggled to completely eliminate Hamas from Gaza, at times returning to parts of the strip to engage in fighting.

Israel’s military says it has killed more than 15,000 Hamas militants in the past year of fighting. Intelligence officials from Arab countries say Israel’s estimate is optimistic and Hamas’s losses, while severe, are closer to 10,000. The group had an armed force of around 25,000 to 30,000 fighters before the war.

If Sinwar is confirmed dead, “it is a very clear leadership setback and yet again showcases the effectiveness of Israel’s military strategy,” said Sanam Vakil, director of the Middle East and North Africa program at Chatham House, a think tank in London.

But, she said, “it doesn’t remove the actual reality on the ground where Hamas and other groups remain” opposed to Israel and will continue to fight its military in the absence of a political process.

As Israel has taken out Hamas’s military capabilities, its military has shifted in recent weeks to focus on an air-and-ground operation against Hezbollah in Lebanon. The Lebanese military group began firing rockets and missiles on Israel a day after Hamas sparked the war in Gaza, causing the displacement of tens of thousands of people on both sides of the Israeli-Lebanese border.

Israel’s campaign has killed Hezbollah’s leader and other officials, as well as a senior Iranian military commander. In response, Iran launched a ballistic-missile assault earlier this month on Israeli territory and Israel is expected to mount an attack against Iran in retaliation.

It’s not clear whether Sinwar’s death will change Israel’s thinking about an attack on Iran.

Given Israel has killed much of Hamas’s military and political leadership, Netanyahu is likely to face pressure to re-engage in cease-fire talks in Gaza that could now lead to the return of hostages held there.

A forum representing the families of hostages held in Gaza said in a statement Thursday that it is worried about the fate of the remaining hostages and that it demands “to leverage the military achievement for an immediate deal for their return.”

Write to Rory Jones at Rory.Jones@wsj.com, Summer Said at summer.said@wsj.com and Anat Peled at anat.peled@wsj.com