Children are being used as porters, guards, informers and fighters and, in some cases, as human shields, the charity said in Childhood Under Fire.
Some two million children are in need of assistance in Syria, Save the Children estimates.
It says the two-year conflict has affected all aspects of their lives.
Researchers from Turkey found that three in every four Syrian children they interviewed had lost a loved one because of the fighting, the report says.
Many have lost access to healthcare and are living in unsanitary conditions where the risk of disease is high. Their families are struggling for food as shortages send prices beyond the reach of poorer families.
Their education has been disrupted as some 2,000 schools have either been damaged by the fighting or become temporary shelters for displaced people.
Syria’s children are the conflict’s “forgotten victims – facing death, trauma and suffering, and deprived of basic humanitarian aid”, the report said.
Save the Children has appealed for international help, but said: “The only way to stop their suffering is to bring an end to the war.”
The report said it had found a growing pattern of children under the age of 18 being used by armed groups on both sides in the conflict.
For many children and their families, it is seen as a source of pride, the report says, but some children are being forcibly recruited into military activities.
In some cases, children as young as eight have been used as human shields, the report says.
One group affiliated to the opposition has documented the deaths of at least 17 children associated with armed groups since the start of the conflict; many others have been severely injured and in some cases permanently disabled, the report also says.
The research team at Bahcesehir University in Turkey found that not only had three in every four children they spoke to had lost a loved one, but one in every three children had been hit, kicked or shot at in the course of the conflict.
“I don’t think there is a single child untouched by this war,” the report quotes a child called Safa as saying.
“Everyone has seen death, everyone has lost someone. I know no one who has not suffered as we have. It is on such a scale.”
The Save the Children report echoes similar findings made public by the UN children’s agency Unicef on Tuesday.
Unicef warned of a lost generation in Syria, saying children under the age of 18 were growing up knowing nothing but violence, were being deprived of a right to an education and were suffering traumas that could scar them for life.
As many as 70,000 people have died in the two-year conflict, the UN believes.
More than a million Syrians have now been registered as refugees by the UN in neighboring countries.
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