The dead included one of the bodyguards of the 60-year-old Hariri, who resigned as prime minister four months ago in a row over Syrian dominance of Lebanon.
The attack plunged Lebanon into grief and raised worries about the stability of the country, which is treading a delicate path between its Sunni, Shia and Christian communities.
It came at a time of high political tension in Lebanon and international pressure over Syria's role in the country, just a few months before legislative elections are due to be held.
Lebanese anti-Syrian opposition leaders blamed the Syrian and Lebanese authorities for the killing and called for the withdrawal of Syria's troops and intelligence services.
The attack triggered international condemnation, while Lebanon's former colonial power France called for an international inquiry.
Syria was among the first to condemn the attack. "This odious crime is aimed at striking Lebanese national unity and civil peace," President Bashar al-Assad said.
"This murder today is a terrible reminder that the Lebanese people must be able to pursue their aspirations and determine their own political future free from violence and intimidation and free from Syrian occupation," said White House spokesman Scott McClellan.
Lebanon's pro-Syrian president Emile Lahoud said after a crisis meeting of security chiefs that his political foe had died a "martyr for a united Lebanon", and ordered three days of mourning and a state funeral for Hariri.
"The cowardly attack carried out by criminals shows the depths of the hatred that they have for this country ... and is aimed at destroying its peace and stability."
But Druze MP and former minister Marwan Hamadeh, who himself escaped an assassination attempt in October, was explicit in attributing blame.
"This is a horrible crime and the culprits are well known: they start in Damascus and go through the Lebanese government and the secret service," he told Radio France Internationale.
State-run Tele Liban said more than 350 kilograms of explosives were used in the bombing, bringing down concrete walls, leaving a dozen flaming cars and gouging a crater several metres into the road.
Lebanon's official news agency ANI said Hariri, whose every move in Beirut was normally escorted by tight security, was dead on arrival at the American University Hospital, his body disfigured.
Supporters of Hariri gathered outside his west Beirut mansion, weeping and banging their heads in grief.
But they also shouted invectives against Syria and the Lebanese government and demanded the withdrawal of some 14,000 Syrian troops from Lebanon.
Several dozen protesters broke windows outside the offices of Syria's ruling Baath party and tried to set it on fire but were stopped by security forces, an AFP photographer said.
As the Lebanese vented their anger, Hariri's family broadcast on his Future television station several appeals for calm.
Beirut had become a safe city since the civil war, when political assassinations were commonplace, but tensions over Syria have mounted in recent months.
UN Security Council Resolution 1559 adopted last September calls for a halt to foreign interference in Lebanon and a withdrawal of foreign troops - a direct message to Syrian troops on Lebanese soil.
Foreign Minister Mahmud Hammud called an emergency meeting of the ambassadors of the 15 of the Security Council late Monday, his office said.
A previously unknown group - An-Nosra wal Jihad fi Bilad al-Sham - claimed responsibility for the bombing and pledged further attacks on "infidels".
The group, in a videotape shown on Al-Jazeera television, said it carried out a suicide attack "because of his (Hariri's) close ties with the Saudi authorities", but provided no proof of the claim. Hariri's rise was a rags to riches story. Born to a poor farmer in the southern city of Sidon, he became one of the world's 100 richest people credited with spearheading Lebanon's post-war reconstruction.
He headed five governments from 1992, but later became a thorn in the side of Beirut's political masters in Damascus and resigned as premier in October after disputes with the pro-Syrian president.