Within hours of the coordinated attacks, which saw gunmen ambush a bus, detonate a bomb under a military jeep, and fire an RPG at a civilian car, Israeli troops had hunted down and killed seven of the attackers, a top military official said.
And shortly afterwards, Israel hit back at the Gaza-based militant group it accused of responsibility for the attacks, launching air raids that killed six people in a house in the southern city of Rafah, medics said.
Among the dead was the head of the Popular Resistance Committees, and two other senior members of the group, which the military said was behind Thursday's bloodshed in the southern Negev desert.
The attacks began around noon, with two incidents on route 12, a desert road which flanks the Egyptian border, some 25 kilometres (15 miles) north of Eilat.
In the first incident, gunmen strafed a bus, injuring 14 people; shortly afterwards, they detonated a roadside bomb as a military vehicle rushed to the scene, injuring several soldiers.
Security sources told AFP of a third incident on another desert road near the Jordanian border, in which an RPG was fired at cars driving near Beer Ora, some 15 kilometres (nine miles) north of Eilat.
Medics said all seven victims died in the third attack, including four travelling in the same car, and unconfirmed reports suggested militants had also fired mortars in the area.
There were also unconfirmed reports that an anti-tank missile had been fired into Israel from across the border in Egypt.
Security sources initially told AFP that gunmen in a car had opened fire on a bus, and suggested the attackers may have fired from the Egyptian side of the border. But the army later told AFP "everything took place in Israeli territory."
Israeli troops quickly locked down the area and engaged in a running gunbattle with the militants that ended with seven of the attackers killed, the head of the army's southern command told a press conference.
Major-General Tal Russo said two were shot dead in Israeli territory while a third blew himself up with explosives strapped to his body.
Four more were killed on the Egyptian side of the border -- two shot dead by Israeli troops firing across the border, and another two shot by Egyptian forces, he said.
In a post on Twitter, military spokeswoman Avital Leibovich said several of the militants had been armed with explosive belts. "Some of the terrorists involved in today's attack on Israelis carried explosive belts and grenades," she wrote.
Israel quickly blamed the bloodshed on militants from the Hamas-run Gaza Strip and vowed to hit back hard.
Israeli Defence Minister Ehud Barak said the "source" of the attacks was in Gaza, and vowed "to act against them with all our strength and determination."
"The incident reflects the weakness of the Egyptian hold on Sinai and the expansion of activity there by terror elements," he said.
Several hours later, he confirmed that the air force had hit the Popular Resistance Committees -- the group which the military said was behind the attacks.
"An IAF aircraft targeted senior militants of the Popular Resistance Committees terrorist organisation in the southern Gaza Strip," an army statement said, naming three of the group's leaders.
"These officials were behind today's combined terrorist attacks with the primary objective of kidnapping an Israeli civilian or soldier."
Israeli Prime Minister Benjamin Netanyahu said the attacks had "damaged Israel's sovereignty," while his spokesman said Israel had "concrete information" that the attackers had come from Gaza.
Another Israeli official, speaking on condition of anonymity, said the attackers had entered Israel from Sinai, which they had crossed into from Gaza.
World leaders were quick to condemn the violence, with the White House denouncing the "brutal terrorist attacks," and urging Egypt to follow through on pledges to ensure security in the Sinai.
UN leader Ban Ki-moon also issued a strong condemnation of the bloodshed, and expressed concern about an "escalation" of violence in the region where Egyptian troops are pressing a major operation in northern Sinai to rein in militant groups.