Riad Hijab - who planned the break for months, according to an aide - is the highest-level political figure to switch sides and is certain to encourage rebels after a string of military and diplomatic figures abandoned the regime. A Jordanian official and a rebel spokesman said he fled to Jordan.
A senior U.S. official said the defection is more evidence that the Assad regime "is crumbling." The official, traveling with U.S. Secretary of State Hillary Clinton in Johannesburg, urged other senior members of the government and military to break with Assad.
The Syrian regime has suffered a series of significant setbacks over the past month that point to a loosening of its grip on the country.
Four of the president's top security aides were killed in a rebel bombing of state security headquarters in the capital Damascus on July 18, including the defense minister and Assad's brother in law. There has been a steady stream of high-level defections from diplomats to generals. And the regime has been unable to fully subdue rebel challenges in the two major cities, Damascus and Aleppo.
But power remains closely held within Assad's inner circle and even posts such as the prime minister have limited clout. Because he is not part of that elite, Hijab's departure will not immediately undercut the regime's ability to fight rebels in places such as Aleppo, Syria's largest city, which has been pounded by gunners and warplanes.
Still such defections carry symbolic importance and highlight that dissent reaches into the upper levels of government even though they still have not cracked the pillars of Assad's rule that include the military and his minority Alawite community.
Hijab is part of Syria's Sunni majority, which forms the bedrock of the opposition in the 17-month-uprising that has claimed at least 19,000 lives.
Just hours before word of the defection got out, Assad suffered another blow in his attempt to portray he is in control: A bomb ripped through the third floor of the state TV building in Damascus, wounding at least three employees and displaying the ability of rebels to strike in the heart of the capital.
Mohammad Otari, Hijab's spokesman, told The Associated Press in Amman, Jordan that the minister was appointed about two months ago and started planning his defection at that time. He said Hijab rebels from the Free Syrian Army at least two months ago to help him escape, which they did.
"The criminal Assad pressed him to become a prime minister and left him no choice but to accept the position. He had told him: 'You either accept the position or get killed,'" said Otari, who told the AP that Hijab and his family planned to travel on from Amman to Qatar, one of the main state backers of the rebels.
"The prime minister defected from the regime of killing, maiming and terrorism. He considers himself a soldier in the revolution," the aide said.
Otari said Hijab, who hails from Syria's eastern province of Deir el-Zour, was in a "safe place" along with his family and seven brothers, including two who held top government posts at the ministries of oil and environment. He did not say where they were.
A former agriculture minister, Hijab was considered a loyalist in Assad's ruling Baath party.
Ahmad Kassim, a senior official with the Free Syrian Army, said Hijab defected to Jordan along with two other ministers. But there has been no confirmation from Syria or anywhere else on other ministers defecting.
A Jordanian government official confirmed Hijab defected with his family, but did not comment on whether other ministers had also come. The official spoke on condition of anonymity, saying he was not allowed to make any public statements on the defection.
Jordan's Information Minister Sameeh Maaytah's denied that Hijab had "defected" to Jordan, but the statement appears to reflect the kingdom's concern over further angering its more powerful neighbor. Jordan is already giving refuge to 140,000 Syria refugees.
The other ministers' identities were not immediately known and Syrian TV denied reports that Finance Minister Mohammad Jlailati had defected or been jailed.
The Syrian opposition celebrated Hijab's defection and saluted his bravery. George Sabra, a spokesman for the opposition Syrian National Council, said Hijab is a symbol of the state and added that he expected his desertion to usher in a chain of others.
"He has finally discovered that this regime is an enemy of its own people and is destined to fall, and he chose to join the ranks of those who defected before him," Sabra told AP. "This will trigger a chain of other defections by Syrian senior government and security officials," he added. "The Syrian regime is drowning and this is the clearest sign yet."
Clinton plans to stop in Turkey for meetings on Syria on Saturday. The blasts at the state TV offices raised issues likely to be part of her talks: The apparent ability the rebels to strike key sites in Damascus and the regime's increasing finger-pointing at countries that have sided with the opposition.
Ahmad Abdullah, a Turkey-based member of the Free Syrian Army rebel group, said the state TV station that was attacked "broadcasts government propaganda and this makes it a target for the rebels."
A pro-government private Syrian TV station, Al-Ikhbariya, broadcast images of the damage at the state TV building. The footage showed destroyed walls, overturned desks, blown-out cabinet doors, broken glass and dangling electricity cables. A few TV workers were shown tending to a wounded colleague.
Information Minister Omran al-Zoubi blamed Qatar, Saudi Arabia and Israel for the attack. Syrian authorities accuse the Gulf countries and Israel of supporting the rebels.
"Nothing can silence the voice of Syria or the voice of the Syrian people," al-Zoubi said while inspecting the damage at the TV building. "We have a thousand locations to broadcast from."
Syria's rebels have grown increasingly bold and capable in recent months. In July, the rebels and Syrian regime forces fought intense battles for a week in Damascus in what was the opposition fighters' biggest challenge so far in the capital.
The government claimed Saturday it was now in full control of all districts in the capital, after purging one of the last rebel-held areas, but clashes have continued in some districts.
In a brazen daylight attack, rebels commandeered a bus and snatched 48 Iranians just outside Damascus Saturday. Iran said those abducted were pilgrims who were visiting a shrine about 10 miles (six kilometers) south of Damascus and were on their way to the airport to return home.
But the captors claimed in a video broadcast Sunday that one of the captives was an officer of Iran's powerful Revolutionary Guards and that the 48 were on a "reconnaissance mission" in the capital.
Mainly Shiite Iran is a close ally of the beleaguered Syrian government, which is dominated by the minority Alawite sect, an offshoot of Shiite Islam.