President Bashar al-Assad's regime "is butchering its own people. The history of Homs is being written in the blood of its citizens," Cameron told a news conference at the close of an EU summit.
European leaders also issued a strong new call for the perpetrators of the violence in Syria to be brought to book.
Describing the situation in Homs as "truly terrible", with residents under constant shelling, with no water, no food and no medicine, he said: "It is a scene of medieval barbarity."
"The world must come together to condemn the killing. So I say to the Russians and to the Chinese: look hard at the suffering from Syria and think again about supporting this criminal regime."
Russia and China have angered the West by vetoing UN Security Council resolutions on Syria, where the UN says more than 7,500 people have been killed since the regime launched a brutal crackdown on protests almost a year ago.
"We will make sure, as we did in Serbia, that there is a day of reckoning for those who are responsible," Cameron said, referring to the war crimes trial of dead Serbian strongman Slobodan Milosevic.
"So I have a clear message for those in authority in Syria: turn your back on this criminal regime or face justice for the blood that is on your hands."
His call came as EU leaders, "horrified" by the atrocities taking place in Syria, issued a joint call for those responsible to be held to account.
EU president Herman Van Rompuy said the 27 EU leaders had adopted a text stating that "the European Council remains determined to ensure that those responsible for atrocities in Syria are held accountable for their actions".
The bloc would work closely with those working to record "these appalling crimes", the EU leaders said in their summit conclusions.
"We are horrified by the atrocities that have been committed and are still being committed," Van Rompuy said.
He spoke as French President Nicolas Sarkozy announced the closure of his country's embassy in Syria due to the "scandalous" repression of opponents to Assad's regime.
EU leaders also pledged to tighten the noose on Assad's regime with fresh sanctions as diplomatic pressure mounted on Damascus to bring an end to the violence.
"I think we should focus on those things we can do in terms of building the strongest possible political and diplomatic alliance to pressurise this regime," said Cameron.
"So, further rounds of sanction, further help for the opposition, further work with the opposition to increase their focus and their appeal to all of Syria," he added.