"Inside Syria, 765,000 children under the age of five live in hard-to-reach areas where conflict and restriction make it extremely difficult to reach them with humanitarian assistance including regular access to vaccines," UN agencies said.
Polio is a potentially fatal viral disease that half a century ago killed or crippled hundreds of thousands of people, mainly children, most famously US president Franklin D. Roosevelt.
In 1988, the disease was endemic in 125 countries, and 350,000 cases were recorded worldwide, according to UN figures.
The UN agencies said polio had struck again in Syria after a 14-year absence because the civil war had disrupted what had been routine childhood immunisations, with millions fleeing their homes.
Polio vaccination coverage in Syria has declined from an average of 99 percent to 52 percent, they said.
At least 60 percent of Syria?s hospitals have been destroyed or damaged, and less than a third of public ambulances are still functional.
We got to a point where we had to work with very limited resources to defeat what had been a long forgotten enemy in this region", said World Health Organization polio specialist Chris Maher.
He warned that the disease is "one that does not know borders or checkpoints and can travel fast, infecting children not just in war-torn Syria but across the region".
More than 6.5 million children are now in need of assistance, according to the UN agencies, which urged access for aid workers to children trapped in war zones inside Syria.
"Our job is far from over. In the coming months, we have to reach more and more children, especially those who have not been reached because of the insecurity and violence," said Maria Calivis, Middle East director of the UN children's agency UNICEF.
The UN agencies said they had completed the first phase of the biggest polio vaccination campaign they had ever undertaken in the Middle East, reaching 25 million children under the age of five.