Syrian rebels said Damascus was "now free of Assad".
Earlier the leader who crushed all forms of dissent flew out of Damascus for an unknown destination on Sunday, two senior army officers told Reuters, as rebels said they had entered the capital with no sign of army deployments.
Thousands in cars and on foot congregated at a main square in Damascus waving and chanting "Freedom" from the long Assad family rule, witnesses said.
"We celebrate with the Syrian people the news of freeing our prisoners and releasing their chains and announcing the end of the era of injustice in Sednaya prison," said the rebels.
Sednaya is a large military prison on the outskirts of Damascus where the Syrian government detained thousands.
A Syrian Air plane took off from Damascus airport around the time the capital was reported to have been taken by rebels, according to data from the Flightradar website.
The aircraft initially flew towards Syria's coastal region, a stronghold of Assad's Alawite sect, but then made an abrupt U-turn and flew in the opposite direction for a few minutes before disappearing off the map.
Reuters could not immediately ascertain who was on board.
The head of Syria's main opposition group abroad, Hadi al-Bahra, on Sunday also declared that Damascus is now "without Bashar al-Assad".
As Syrians expressed joy, Prime Minister Mohammad Ghazi al-Jalali said he is ready to support the continuity of governance and is prepared to cooperate with any leadership chosen by the Syrian people.
The frontlines of Syria's complex civil war were dormant for years. Then Islamists once affiliated with Al Qaeda suddenly burst into action, posing the biggest challenge to Assad, who had survived years of gruelling war and international isolation with the help of Russia, Iran, and Lebanon's Hezbollah.
But his allies were focused on and weakened by other crises, suddenly leaving Assad at the mercy of his opponents.
Just hours before reaching Damascus, rebels announced they had gained full control of the key city of Homs after only a day of fighting, leaving Assad's 24-year rule dangling by a thread.
Thousands of Homs residents poured onto the streets after the army withdrew from the central city, dancing and chanting "Assad is gone, Homs is free" and "Long live Syria and down with Bashar al-Assad".
Rebels fired into the air in celebration, and youths tore down posters of the Syrian president, whose territorial control has collapsed in a dizzying week-long retreat by the military.
The fall of Homs gave the insurgents control over Syria's strategic heartland and a key highway crossroads, severing Damascus from the coastal region that is the stronghold of Assad's Alawite sect and where his Russian allies have a naval base and air base.
Homs' capture is also a powerful symbol of the rebel movement's dramatic comeback in the 13-year-old conflict. Swathes of Homs were destroyed by gruelling siege warfare between the rebels and the army years ago. The fighting ground down the insurgents, who were forced out.
Hayat Tahrir al-Sham commander Abu Mohammed al-Golani, the main rebel leader, called the capture of Homs a historic moment and urged fighters not to harm "those who drop their arms".
Rebels freed thousands of detainees from the city prison. Security forces left in haste after burning their documents.
Syrian rebel commander Hassan Abdul Ghani said in a statement early Sunday that operations were ongoing to "completely liberate" the countryside around Damascus and rebel forces were looking toward the capital.
In one suburb, a statue of Assad's father, the late President Hafez al-Assad, was toppled and torn apart.
Outside the city, rebels swept across the entire southwest over 24 hours and established control.
EXISTENTIAL THREAT TO ASSAD RULE
The pace of events has stunned Arab capitals and raised fears of a new wave of regional instability.
Qatar, Saudi Arabia, Jordan, Egypt, Iraq, Iran, Turkey, and Russia issued a joint statement saying the crisis was a dangerous development and calling for a political solution.
Syria's civil war, which erupted in 2011 as an uprising against Assad's rule, dragged in big outside powers, created space for jihadist militants to plot attacks around the world, and sent millions of refugees into neighbouring states.
Hayat Tahrir al-Sham, the strongest rebel group, is the former al Qaeda affiliate in Syria regarded by the U.S. and others as a terrorist organisation, and many Syrians remain fearful it will impose draconian Islamist rule.
Golani has tried to reassure minorities that he will not interfere with them and the international community that he opposes Islamist attacks abroad. In Aleppo, which the rebels captured a week ago, there have not been reports of reprisals.
When asked on Saturday whether he believed Golani, Russian Foreign Minister Sergei Lavrov replied, "The proof of the pudding is in the eating".
ALLIES' ROLE IN SUPPORTING ASSAD
Assad's long rule relied on allies to subdue the rebels. Russian warplanes conducted bombing while Iran sent allied forces, including Hezbollah and Iraqi militia, to reinforce the Syrian military and storm insurgent strongholds.
But Russia has been focused on the war in Ukraine since 2022, and Hezbollah has suffered big losses in its own gruelling war with Israel, significantly limiting its ability or that of Iran to bolster Assad.
U.S. President-elect Donald Trump has said the U.S. should not be involved in the conflict and should "let it play out".