The Houthi militia in Yemen has vowed to retaliate after President Trump ordered large-scale military strikes on targets controlled by the group that it says killed at least 53 people.

The group, which is backed by Iran, said that women and children were among those killed in the strikes on Saturday, the most significant U.S. military action in the Middle East since Mr. Trump took office in January.

For more than a year, the Houthis have launched attacks against Israel and threatened commercial shipping in the Red Sea in solidarity with their ally Hamas, which led the Oct. 7, 2023, attack on Israel that set off the war in Gaza. The Houthis suspended the campaign in January after a cease-fire was reached in Gaza but have vowed to step up attacks again after Israel instituted a blockade on aid to the enclave this month.

The U.S. airstrikes targeted Houthi-controlled areas across Yemen, including the capital, Sana, as well as Saada, al-Bayda, Hajjah and Dhamar Provinces, according to reports from Houthi-run media channels. The strikes killed at least 53 people and wounded 98, Anis al-Asbahi, a spokesman for the Houthi-run health ministry, said on Sunday.

The casualty figures could not be independently verified, and the United States has not given any estimates for the number of people killed or wounded in the strikes.

On Sunday, Michael Waltz, Mr. Trump’s national security adviser, described the U.S. weekend attacks on Yemen as both successful and effective. “We hit the Houthi leadership, killing several of their key leaders last night, their infrastructure, the missiles,” he said on “Fox News Sunday.” He cast the Houthis as “essentially Al Qaeda with sophisticated Iranian-backed air defenses and anti-ship cruise missiles and drones” that have attacked the entire global economy.

The U.S. Central Command, which posted a video of a bomb leveling a building compound in Yemen, said that Washington had employed precision strikes to “defend American interests, deter enemies and restore freedom of navigation.”

U.S. airstrikes also targeted a power facility in the northwestern town of Dahyan, causing a nightlong electricity blackout, residents said.

A United Nations spokesperson expressed concern about the American strikes while also noting recent Houthi threats to resume attacks on shipping in the Red Sea.

The Houthi-run Al-Masirah television channel reported that 13 people were killed and nine others wounded in airstrikes on al-Jeraf, a district in Sana that is considered a stronghold of the group. In Saada Province, in the northwest, 10 people, including four children, were killed when airstrikes hit two buildings, the report said.

Residents in Sana shared images and videos on social media showing shattered windows and fireballs rising from sites that were struck. Others posted anguished messages as the airstrikes hit.

Abdul Rahman al-Nuerah, a resident of Sana, said the blasts had shattered the windows of his home and terrified his four children. “I instantly embraced and comforted them,” Mr. al-Nuerah said by telephone. “Children and mothers are afraid and still in shock.”

Mohammed al-Bukhaiti, a senior Houthi leader, vowed retaliation against the United States, calling the strikes unjustified. “We shall respond to the escalation by escalating,” he wrote on X.

The Houthi rebels, who control most of northern Yemen, had temporarily halted attacks in the Red Sea when a cease-fire took effect in Gaza in January. But last week, they said they would target any Israeli ships violating their ban on Israeli vessels passing through the Red Sea, the Arabian Sea, the Bab el-Mandeb and the Gulf of Aden.

The Bab el-Mandeb is a strait between the Horn of Africa and the Middle East that connects the Red Sea to the Gulf of Aden, which opens into the Arabian Sea and the Indian Ocean.

Mr. Trump said in a statement on his Truth Social platform that the strikes were also intended as a warning to Iran, the Houthis’ main backer.

“Support for the Houthi terrorists must end IMMEDIATELY!” he wrote. He also warned Iran against threatening the United States, saying, “America will hold you fully accountable, and we won’t be nice about it!”

Some military analysts and former American commanders said on Sunday that a more aggressive campaign against the Houthis, particularly against Houthi leadership, was necessary to degrade the group’s ability to threaten international shipping. “This is long, long overdue,” Gen. Kenneth F. McKenzie Jr., a retired head of the Pentagon’s Central Command, said in a telephone interview on Sunday.

Defense Secretary Pete Hegseth said on Sunday that the United States would conduct an “unrelenting” campaign of strikes against the Houthis until the militant group ceased its actions in the Red Sea.

“This isn’t a one-night thing. This will continue until you say, ‘We’re done shooting at ships. We’re done shooting at assets,’” Mr. Hegseth told Fox News on Sunday. “This campaign is about freedom of navigation and restoring deterrence.”

Iran strongly condemned the strikes.

Esmaeil Baghaei, a spokesman for Iran’s foreign ministry, called them a violation of international law regarding the use of force and respect for national sovereignty.

And Hossein Salami, the commander in chief of Iran’s Revolutionary Guards force, denied on Sunday that his country was making policy decisions for the rebels in Yemen. The Houthi militia “makes its own strategic decisions” and Tehran plays “no role in setting the national or operational policies” of the group, he was quoted as saying by Iranian state news agencies.

Days after taking office, Mr. Trump issued an executive order to redesignate the Houthis a “foreign terrorist organization,” calling the group a threat to regional security.

The order restored a designation given to the group late in the first Trump administration. The Biden administration lifted the designation shortly after taking office, partly to facilitate peace talks in Yemen’s civil war.

Last year, the Biden administration labeled the Houthis a “specially designated global terrorist” group — a less severe category — in response to attacks against vessels in the Red Sea.

Russia’s foreign minister, Sergey V. Lavrov, on Saturday told Secretary of State Marco Rubio that all sides should cease from the “use of force” in Yemen and enter a “political dialogue,” according to the Russian foreign ministry. Moscow has condemned past U.S. and British strikes on Yemen.

Hezbollah, another armed proxy for Iran in the region, voiced its condemnation of the U.S. strikes on Yemen and described it as a “war crime,” according to a statement on Sunday.

Carol Rosenberg, Eric Schmitt and Leily Nikounazar contributed reporting.