Riyad Farid Hijab, appointed premier in June after widely boycotted parliamentary elections, "was given two options -- to either take the office of prime minister or be killed," Hijab spokesman Mohammad Otari told Qatar broadcaster al-Jazeera.
"He had a third option in mind -- to plan his own defection in order to direct a blow to the regime from within," Otari said.
Also defecting was Syria's first man in space, Mohammad Ahmad Faris, and other high-ranking military officers.
"I am ready to provide assistance to the Free Syrian Army," Faris told commanders of the umbrella group of rebel fighters after slipping across the border into Turkey over the weekend, Turkish news agency Anadolu reported. "We are with you all the way."
Faris was part of a 1987 three-man Soviet space mission and is still an active member of the Syrian air force, with the rank of colonel.
While his defection was seen as largely symbolic, that of Hijab can be seen as a significant political strike against the future of the Syrian regime.
The defection of a man widely seen as a dedicated regime loyalist was coordinated with the opposition Free Syrian Army almost from Day One of his appointment, Otari said.
An FSA spokesman confirmed the main armed opposition group, composed of defected Syrian armed forces personnel and volunteers, had organized Hijab's defection and smuggled him with his wife and four children through the desert and across the border into Jordan from southern Syria under cover of darkness early Monday.
Jordanian authorities confirmed the defection to al-Jazeera.
"I announce today my defection from the killing and terrorist regime and I announce that I have joined the ranks of the freedom and dignity revolution," Hijab said in a statement issued in his name in the Jordanian capital Amman.
"I announce that I am from today a soldier in this blessed revolution," the statement said.
It wasn't clear if Hijab would seek a leadership opposition role or if he was simply seeking a haven for him and his family. There were reports other members of his family also defected with him.
Hijab, the highest-level regime official to leave and the regime's highest-ranking Sunni Muslim member, was poised to travel to Doha, Qatar, from Amman, al-Jazeera reported, but no Arab nation commented officially on the issue.
Qatar is a key backer of the Syrian rebels.
Syrian state TV reported Hijab had been fired and was replaced with Minister of Local Administration Omar Ibrahim Ghalawanji, another member of the Sunni majority, who now leads a caretaker government.
Ghalawanji immediately pledged to confront the "conspiracies" facing the country.
Otari flatly denied Hijab had been fired.
In Washington, White House spokesman Jay Carney said Hijab's defection "reinforces that the Assad regime is crumbling from within and that the Syrian people believe that Assad's days are numbered."
The defection reflects on Assad's "inability to maintain any following among the Syrian people that isn't brought about at the point of a gun," Carney said.
U.S. Secretary of State Hillary Rodham Clinton is expected to arrive in opposition supporter Turkey Saturday for meetings on Syria.
Hijab's job wasn't related to the regime's security agencies and he had no role in military operations, analysts said, pointing out that Sunnis may get top civilian posts but Alawites, a Shiite offshoot, control Syria's military and security apparatus.
But even that may be crumbling.
A Syrian brigadier general was among 12 soldiers who fled to Turkey Monday night, said Selcuk Unal, a spokesman for the Turkish Foreign Ministry. Some 1,316 civilians also were part of the exodus.
Turkey is now providing refuge to about 47,500 Syrians, the spokesman said.
"It's humiliating and shows that Assad doesn't know any more on whom he can count," Syrian analyst Rime Allaf at London's Royal Institute of International Affairs think tank, also known as Chatham House, told the British newspaper the Guardian, referring to Hijab's defection.
The defections come less than a month after a bomb attack killed four of Assad's top security officials, including his brother-in-law, Deputy Defense Minister Assef Shawkat, a principal architect of the crackdown on the opposition uprising that began 17 months ago.
Analysts said that attack was a far more devastating blow than Monday's defection.
Ali Akbar Salehi, Iran's foreign minister, is scheduled to visit Turkey Tuesday, and discussions about Syria are expected to be on the agenda.