By Emma Batha-Reuters
More than 850 children were also recruited to fight - more than double the number in 2015 - with some used as executioners and suicide bombers, UNICEF said.
"The depth of suffering is unprecedented. Millions of children in Syria come under attack on a daily basis," the agency's regional director GeertCappelaere said in a statement from Homs in Syria.
"Each and every child is scarred for life with horrific consequences on their health, well-being and future."
At least 652 children were killed last year, up by 20 percent from 2015, the agency said.
The figures - collected since 2014 - only represent formally verified casualties, meaning the true toll could be higher.
UNICEF also said there were at least 338 attacks against hospitals and medical personnel last year.
Half of Syria's pre-war population has been uprooted in the conflict whose six-year anniversary falls on March 15.
Around 6.5 million people are displaced within Syria and nearly 5 million have sought shelter in neighbouring countries where conditions are getting increasingly desperate.
The Norwegian Refugee Council (NRC) said nearly one million were trapped in besieged areas inside Syria with almost no aid.
It said siege and starvation continued to be used as weapons of war and called for an immediate end to all obstacles preventing civilians accessing aid.
"Over the last year in Syria all parties involved have blocked vital aid supplies and millions have become poorer, hungrier and more isolated from assistance and from the world," NRC's Middle East director Carsten Hansen said in a statement.
"We join the rest of the international humanitarian community on this milestone of shame to voice outrage at the plight of millions of civilians living in a downward spiral of despair."
UNICEF said many children were also dying from preventable diseases with the fighting making it difficult to access medical care and lifesaving supplies.
The agency added that Syrian families across the region were taking extreme measures to survive, often forcing children out of the classroom and into early marriage and child labour.
A survey by the International Rescue Committee (IRC) released on Monday suggested Syrian children's mathematics and reading skills were falling far behind pre-war levels.
"... trauma and displacement leave children with emotional scars that can dramatically inhibit their ability learn," said IRC's CEO David Miliband.
"We are storing up huge problems for tomorrow if we do not give Syrian children the resources they need to heal, develop and thrive."
Attention! Any person who sends any financial, legal, criminal, administrative liability content resulting from criminal, illegal, threatening, offensive, insulting, profane, humiliating, degrading, vulgar, pornographic, anti-moral, Member / Member's.