UN Humanitarian chief Stephen O’Brien says about 400 people must be evacuated from a Madaya hospital or risk dying.
Mr O’Brien made the comments after briefing the UN Security Council, as aid was delivered to the besieged area.
He said the patients were "in grave peril of losing their lives."
Trucks carrying food and medical supplies have reached Madaya near the Lebanese border and are beginning to distribute aid as part of an agreement between warring sides.
A UN spokesman said aid trucks were also en route to the Shi'ite villages of al Foua and Kefraya in the northwestern province of Idlib, two other areas where there is a desperate need for humanitarian assistance.
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US ambassador Samantha Power also had strong words about Madaya, slamming the "grotesque starve-or-surrender tactics the Syrian regime is using right now against its own people".
"Look at the haunting pictures of civilians, including children, even babies, in Madaya," she said on Monday.
"These are just the pictures we see. There are hundreds of thousands of people being deliberately besieged, deliberately starved, right now. And these images, they remind us of World War Two."
Power was speaking at a special session of the 193-nation UN General Assembly on the 70th anniversary of the assembly's first meeting in London.
Dozens are said to have died from starvation or lack of medical care in the town and activists say some inhabitants have been reduced to eating leaves.
Images said to be of emaciated residents have appeared widely on social media.
Syrian Ambassador Bashar Ja'afari told reporters his government was committed to "co-operate fully" on aid delivery but said much of what was said about Madaya was "based on false information". He labelled pictures of starving people as "fabrications".
"There is no shortage of humanitarian assistance in Madaya," he said, adding that some aid has been "looted by armed terrorist groups".
However, UN and relief agency workers saw starving people in two besieged Syrian areas where aid deliveries were made, a senior UN official said.
This picture provided by The International Committee of the Red Cross (ICRC), working alongside the Syrian Arab Red Crescent (SARC) and the United Nations (UN), shows a convoy containing food, medical items, blankets and other materials being delivered to the town of Madaya in Syria (ICRC via AP) Source: AAP
"We have seen with our own eyes severely malnourished children. I am sure there also malnourished older people and it is true they are malnourished, and so there is starvation, and I am sure the same is true on the other side in al Foua and Kefyra," he told Reuters by phone from Madaya on Monday.
Foua and Kafyra are two mostly Shi'ite villages, besieged by rebels, that also received deliveries from Monday's convoy.
Offloading aid supplies was expected to last through the night, and the full aid operation several days, the International Committee of the Red Cross said.
Images said to be from Madaya and showing skeletal men with protruding ribcages were published by the Syrian Observatory for Human Rights, a group that monitors the war, while an emaciated baby in a nappy with bulging eyes was shown in other posts.
Madaya residents on the outskirts of the town said they wanted to leave. There was widespread hunger and prices of basic foods such as rice had soared, with some people living off water and salt, they said.
The blockade of Madaya has become a focal issue for Syrian opposition leaders, who told a UN envoy last week they would not take part in talks with the government, slated for later this month, until it and other sieges are lifted.
