The leaders of the US, UK, France, Germany and the EU have all called for Syria's President Assad to step down over his suppression of protesters.
US President Barack Obama said: "The time has come for President Assad to step aside."
It marks a significant increase in pressure on Mr Assad for sending in his army against the protesters.
Meanwhile, UN investigators say the use of violence in Syria "may amount to crimes against humanity".
In a report to the UN Human Rights Council, the investigators said the UN Security Council should refer the issue to the International Criminal Court.
Human rights groups believe about 2,000 people have been killed and thousands arrested since March as Syria's security forces - including tanks, helicopters, gunships and snipers - try to quell dissent that has broken out in much of the country.
President Bashar al-Assad has promised political reforms but has continued to clamp down on the protesters, blaming the unrest on "terrorist groups".
'Get out of the way'
In a written statement, Mr Obama said: "The future of Syria must be determined by its people, but President Bashar al-Assad is standing in their way. His calls for dialogue and reform have rung hollow while he is imprisoning, torturing, and slaughtering his own people.
He added: "We have consistently said that President Assad must lead a democratic transition or get out of the way. He has not led. For the sake of the Syrian people, the time has come for President Assad to step aside."
Mr Obama also announced "unprecedented sanctions to deepen the financial isolation of the Assad regime and further disrupt its ability to finance a campaign of violence against the Syrian people".
The US had already tightened its sanctions against members of Syria's government but had stopped short of demanding Mr Assad step down.
At the same time, the EU and the leaders of Britain, France and Germany issued statements also calling on President Assad to leave.
European Union foreign policy chief Catherine Ashton said: "The EU notes the complete loss of Bashar al-Assad's legitimacy in the eyes of the Syrian people and the necessity for him to step aside."
In a joint statement, the leaders of Britain, France and Germany said President Assad should "leave power in the greater interests of Syria and the unity of his people".
Canadian Prime Minister Stephen Harper joined the other leaders in calling on "President Assad to vacate his position, relinquish power and step down immediately".
A Syrian government spokesman accused Western governments of increasing the tension in the country.
"It is strange that instead of offering [Damascus] a helping hand to implement its programme of reforms, the West and Obama are seeking to stoke more violence in Syria," Reem Haddad, of the information ministry, told AFP news agency.
The new sanctions announced by Mr Obama included a freeze on all assets of the Syrian government subject to US jurisdiction and a ban on US residents from carrying out any transactions with the Syrian government or blacklisted individuals.
Syria's petroleum industry is also subject to the US sanctions.
US Secretary of State Hillary Clinton said the sanctions would "further tighten the circle of isolation" and "strike at the heart of the regime".
The calls for Mr Assad to step down follow a report from UN investigators into the recent violence in Syria.
Their 22-page report says that security forces, including snipers, have used deadly force against civilians in attempts to quell months of anti-government protests.
News agencies said the investigators discovered that 26 men were blindfolded and shot dead while in government custody.
In other cases, security forces allegedly killed wounded civilians by putting them alive in refrigerators in hospital morgues, Reuters news agency said.
The UN's investigators were not allowed into Syria. They interviewed victims and witnesses of the violence, some in Syria, and others in the region.
"The mission found a pattern of human rights violations that constitutes widespread or systematic attacks against the civilian population, which may amount to crimes against humanity," the UN investigators said.
The report, released in Geneva, urged the UN Security Council to "consider referring the situation in Syria to the International Criminal Court".
The UN High Commissioner for Human Rights, Navi Pillay, briefed the Security Council on the report later on Thursday in a special session.
After the session, the UN's Under-Secretary General for Humanitarian Affairs said a UN mission would visit Syria from this weekend to investigate the effects of the crackdown.
"We have been guaranteed that we will have full access to where we want to go," she said. "We will want to concentrate on those places where there have been reports of fighting."
An emergency session of the UN Human Rights Council will be held on Monday following a request from all 24 members - including Jordan, Kuwait, Qatar and Saudi Arabia.