Lindsey German, the convenor of Stop the War, told the crowd: "We are here to say one very simple thing: don't bomb Syria.
"Do not this time go and bomb a country where you make it even worse than it was before."
Salma Yaqoob, the head of the Birmingham Stop the War coalition, said "we don't seem to have learned a single thing" from the invasion of Iraq.
"When we bomb other people's countries, we do not become more safe. We become less safe.
"If you bomb them we will not be safe at home."
The emergency protest was called by the Stop the War coalition ahead of Wednesday's vote on airstrikes.
The coalition had condemned as "deplorable" Jeremy Corbyn's decision to grant a free vote to Labour MPs, with Andrew Murray, the group's chairman, saying it had "cleared the way" for the Commons vote on air strikes.
More than 3,500 people said they were going to the event on Facebook, where organisers wrote: "We must do everything we can to stop MPs voting the UK into its fourth war on a Muslim country in 14 years."
A statement on the Stop the War website read: "Britain has been the most aggressive country in Europe over the last 15 years, leading military interventions in Afghanistan, Iraq and Libya.
"Yet it has done little to help the victims of the wars it so enthusiastically pursues and it has been at the forefront of opposing a humane policy towards refugees.
"Another destructive bombing campaign is no solution whatsoever. It will make moves toward a political solution harder. It risks intensifying and widening what is already a catastrophic war."
An entirely peaceful march turned into a sit-down protest outside the Houses of Parliament, with hundreds refusing to move as traffic built up.
Protesters chanted "David Cameron, shame on you" and "Stop the killing, stop the hate" on the road, which is next to Westminster Bridge.
"The police are going to try and intimidate you," a protester told the crowd, while police attempts to move people were largely ignored.
Tuesday's protest comes after thousands of people protested outside Downing Street on Saturday. Parts of Whitehall were brought to a halt during the event, which included speakers such as the actor Mark Rylance and the musician Brian Eno.
A statement issued by more than 50 student leaders was issued earlier on Tuesday. It read: "British military action will not defeat Isis and risks increasing the terrorist threat both to the peoples of the Middle East and to Britain."
SNP MP Philippa Whitford said: "If we drop more bombs all we will do is create more refugees. We do not have Daesh-seeking missiles."
Caroline Lucas, who was given a raucous welcome, said: "It is clear a huge number of civilians will be caught up if we start bombing.
"If we start bombing nobody will be happier than Isis.
"We want to end British arms sales to the Middle East, stop cosying up to Saudi Arabia, pressure Turkey to stop buying oil from Isis."
Richard Burgon MP said: "Britain needs to look at what our Nato ally Turkey is doing and what our ally Saudi Arabia are doing.
"British planes and boots on the ground will hinder, not help.
"It is not too late for MPs to think again. It is not too late to do the right thing."
Imran Hussain, MP for Bradford East, said: "The people of Bradford sent me and the people of Bradford expect me to stand up and be counted. I bring solidarity from the north of England. Let not history repeat itself."
George Galloway said: "This latest war, if it happens, cannot possibly go well."
He said MPs' phones are "ringing off the hook" with constituents urging them to vote against air strikes.
"We may yet be able to deprive David Cameron of a majority. Tell them (the MPs) we are demanding they say no to war on Syria.
"This is a war that even right-wing personalities know is ill-conceived, ill-intentioned and ill-fated."
David Gillespie, a 29-year-old medical student, said: "We could be sanctioning Saudi Arabia and Turkey. It's far too early to be thinking about bombing."