Israeli warplanes struck the Houthi-controlled Yemeni port of Hodeida Saturday, killing at least three people and wounding another 87 according to health authorities.
It comes a day after a drone attack by the Iran-backed rebels killed a civilian in Tel Aviv, both sides said.
The strikes, which triggered a raging fire and plumes of black smoke, are the first claimed by Israel in the Arabian peninsula's poorest country, some 2,000 kilometres (1,300 miles) away, analysts said.
"The blood of Israeli citizens has a price," Israeli Defence Minister Yoav Gallant said, adding more operations against the Houthis would follow "if they dare to attack us".
Gallant said the Hodeida strikes were also a warning to other Iran-backed armed groups around the Middle East that have claimed attacks on Israel during the war on Gaza.
"The fire that is currently burning in Hodeida, is seen across the Middle East and the significance is clear," he said.
Israeli Prime Minister Benjamin Netanyahu echoed the warning in a televised address. "Anyone who harms us will pay a very heavy price for their aggression," he said.
Just hours after Friday's strike in Tel Aviv, Gallant had vowed Israel would retaliate against the Houthis, who control swathes of Yemen, including much of its Red Sea coast.
Israeli military spokesman Daniel Hagari said F-15 jets carried out the strike and all returned safely to base.
Rear Admiral Hagari accused the Houthis of using Hodeida "as a main supply route for the transfer of Iranian weapons... like the (drone) that was used in the attack on Friday."
In a statement on social media, top Houthi official Mohammed Abdulsalam reported a "brutal Israel aggression against Yemen".
The attack targeted "fuel storage facilities and a power plant" in Hodeida "to pressure Yemen to stop supporting" Palestinians in the Gaza war, he said.
The Houthi-run health ministry had initially said at least 80 people were wounded in the Israeli strikes, most of them with severe burns. It did not immediately report any deaths.
An AFP correspondent in Hodeida reported hearing several large explosions and seeing smoke over the port.
Footage aired by the rebels' Al-Masirah television, which AFP could not independently verify, showed casualties being treated in hospital, many of them bandaged and lying on stretchers in packed rooms.
A man interviewed by the broadcaster said many of the wounded were port employees.
"The city is dark, people are on the streets, petrol stations are closed and seeing long queues," said a Hodeida resident, who spoke on condition of anonymity citing safety concerns.
Maritime security firm Ambrey said it observed four merchant vessels in the port at the time of the airstrike and another eight in the anchorage.
"No damage to merchant vessels has been reported at this time," it said.
The United States, which along with Britain has carried out several rounds of airstrikes against the Houthis in an attempt to put an end to their attacks on shipping in the Red Sea, said it played no part in Saturday's strikes.
"The United States was not involved in today's strikes in Yemen, and we did not coordinate or assist Israel with the strikes," a US National Security Council spokesman said.
"We've been in regular and ongoing contact with the Israelis following the strike in Tel Aviv that killed an Israeli civilian on Friday morning. We fully recognise and acknowledge Israel's right to self-defence."
UN chief Antonio Guterres had appealed for "maximum restraint" after the Tel Aviv drone strike to avoid "further escalation in the region".
But Houthi politburo member Mohammed al-Bukhaiti swiftly threatened revenge for the Hodeida strikes.
"The Zionist entity will pay the price for targeting civilian facilities, and we will meet escalation with escalation," he said in a post on social media.
The Houthis' Lebanese ally, Hezbollah, warned that the Israeli strikes on Hodeida marked a dangerous turn nine months into the Gaza war.
"The foolish step taken by the Zionist enemy heralds a new, dangerous phase," said the group, which has exchanged nearly daily fire with the Israeli army throughout the war.
Hodeida port, a vital entry point for imports and international aid for rebel-held areas of Yemen, had remained largely untouched through the decade-long war between the Houthis and the internationally-recognised government propped up by neighbouring Saudi Arabia.
The war has left millions of Yemenis dependent on aid supplied through the port.
"Traders now fear that this will exacerbate the already critical food security and humanitarian situation in northern Yemen, as the majority of trade flows through this port," said Mohammed Albasha, senior Middle East analyst for the US-based Navanti Group.