“I believe Eastern Ghouta cannot wait,” Antonio Guterres told the UN Security Council on Wednesday.
The Eastern Ghouta has been under fierce bombardment from government forces backed by Russian airpower in recent days.
The region is the last major rebel-held area near the capital Damascus.
The Syrian military says it is trying to liberate the area from what it terms terrorists – but it has also been accused of targeting civilians.
“This is a human tragedy that is unfolding in front of our eyes and I don’t think we can let things go on happening in this horrendous way,” Mr Guterres said.
He said an end to the fighting would allow the evacuation of hundreds of people who require urgent treatment as well as allowing humanitarian aid to reach the region.
A draft UN Security Council resolution, proposed by Kuwait and Sweden, is calling for a 30-day ceasefire, but the BBC’s UN Correspondent Nick Bryant says Russia may not allow it to pass.
Russia says it wants an urgent Security Council meeting to discuss the situation, but western diplomats view this as a delaying tactic to give the Syrian military more time to continue its offensive, our correspondent says.
Moscow, which supports the Syrian government, said peace talks with the rebels had failed on Wednesday.
Meanwhile Iran, another Syrian government ally, says it is in close contact with Syria, Russia and Turkey to try to reduce tension in the Eastern Ghouta.
Deputy Foreign Minister Abbas Araghchi told the BBC’s Lyse Doucet that Iran believed in a political solution to the conflict, not a military one.
UN human rights commissioner Zeid Raad Al Hussein has also joined calls for an end to the conflict in the region.
“How much cruelty will it take before the international community can… take resolute, concerted action to bring this monstrous campaign of annihilation to an end?” he said in a statement.
Pro-government forces, backed by Russia, intensified their efforts to retake the last major rebel stronghold on Sunday night.
A doctor working in the region says the situation is “catastrophic” – and he believes the international community has abandoned the people living there.
“They targeted everything: shops, markets, hospitals, schools, mosques, everything,” Dr Bassam told the BBC on Wednesday.
“Maybe every minute we have 10 or 20 air strikes… I will treat someone – and after a day or two they come again, injured again.”
“Where is the international community, where is (the UN) Security Council? … they abandoned us. They leave us to be killed,” he said.
The UN says at least 346 civilians have been killed and 878 have been injured, mostly in airstrikes.
But they say precise figures are still difficult to establish.
The Union of Medical Care and Relief Organizations (UOSSM), which operates medical facilities in the Eastern Ghouta, says 70 people were killed on Wednesday, bringing the total to 366. (Courtesy BBC)