Hariri was traveling in a motorcade in central Beirut when an apparent car bomb detonated.
At least eight other people were killed in the massive blast and 100 wounded, news agencies reported.
There was no immediate official reaction from the government.
President Bashar al-Assad of neighboring Syria quickly condemned the attack as a "terrible criminal act."
Arab League Secretary-General Amr Musa called it a "heinous crime."
"I am so sad that we lost Rafiq Hariri, a great Arab leader and a Lebanese figure of a very respectable stature, who spent his life serving Lebanon, serving the Arab world and the Arab common causes and the common Arab interests," Musa said. "It's a heinous crime."
Lebanese media said Hariri was still alive when he was pulled from the wreckage but that he died on the way to the hospital.
The force of the explosion gouged a deep crater in the road, severely damaged nearby buildings, and set cars ablaze.
Correspondents in the Lebanese capital said it appears Hariri was the target of a deliberate assassination, although it is unclear who may have wanted to kill him. There were no immediate claims of responsibility.
Hariri was a Sunni Muslim and political liberal who came to power in the aftermath of the 15-year civil war that ended in 1989. He is credited with leading the reconstruction of Beirut after the ravages of the war.
He resigned in October after Syria forced him and parliament to change the constitution to allow the Lebanese president to stay in office another three years. On his resignation, Hariri said he wanted Lebanon to be a democratic country and one that would find its own way forward.
He recently called on Syria to remove its 20,000 troops from Lebanon.
Some speculated the attack might also have been aimed Hariri's business interests. He was a multimillionaire real-estate developer who also had a stake in the computer industry.
(AP/AFP)[For more on the regional implications of events in Lebanon, see "Implications Of New International Consensus On Lebanon" in "RFE/RL Iran Report".]