The deep divisions in the House of Commons showed the Prime Minister is now highly unlikely to get the backing of MPs for any intervention when they are due to vote next week on possible military action.
The vote on the UK Government motion backing the principle of military action was lost by 285 votes to 272 - a majority of 13.
It came after Labour's amendment, which called for compelling evidence of the Assad regime's culpability for last week's chemical attack before any military action took place - was also defeated by 220 votes to 332, a majority of 112.
MPs expressed shock at the outcome of the debate. Labour's Dame Joan Ruddock said it was a very important day for democracy in the UK, but added: "Mr Cameron has completely misjudged his own party."
The votes took place as a bitter row broke out over the Tory claim that Labour was "giving succour" to the Assad regime by not backing its call for military action.
Labour leader Ed Miliband's office fired off a complaint about Craig Oliver, the Prime Minister's chief spin doctor, after he accused the Labour leader of potentially "giving succour" to Syrian President Bashir al Assad by delaying a decision on UK involvement in a military response.
Mr Miliband's office sent a letter to Sir Jeremy Heywood, the Cabinet Secretary, condemning his "infantile and irresponsible" comments.
However, Defence Secretary Philip Hammond later repeated the allegation, saying: "Anything that stops us from giving a clear united view of the British Parliament tonight will give some succour to the regime."
Tory high command is furious with Mr Miliband, accusing him of "flip-flopping" on military action with once source branding him a "s***".
Labour denounced the insults as "demeaning to Downing Street".
It was Mr Miliband's insistence that a decision on UK involvement should await the UN inspectors' report that forced Mr Cameron to water down his motion to concede the point and pledge a second vote on whether Britain engaged in military action.
Illustrating the extent to which the Prime Minister still has to convince his own colleagues, David Davis, a senior Tory backbencher, said there was not yet a case for intervention, saying there was "lots more to discover; until we do that we should not be attacking".
As rival groups protested outside the Commons, inside Mr Cameron, opening an impassioned debate, said there was not "one smoking piece of intelligence" but insisted he was convinced by the evidence that it was beyond doubt Assad's regime was responsible for the poison gas attack.
Earlier, No 10 had published a report from the Joint Intelligence Committee, which said it was highly likely the Syrian Government, which had launched 14 chemical attacks since 2012, was responsible for last week's attack, stressing there were no plausible alternative scenarios to regime responsibility.
It also released a summary of the Coalition's legal advice, which said Britain could take action without United Nations approval on the basis of humanitarian intervention.
Discussions on Britain's new resolution at the UN, calling for power to undertake all necessary measures to prevent further chemical attacks in Syria continued. But Whitehall expects Russia to veto it.