"A thousand Syrians who have fled war, most of them children, are stuck in the Moroccan cities of Nador and Beni Enzar waiting for the Moroccan police to let them enter Melilla," a Spanish territory bordering northern Morocco, the charity said in a statement.
It urged the Spanish government to order its consulate in Nador to issue humanitarian permits for the Syrians to cross the nearby border into Melilla.
A fenced-off Spanish city of 80,000 inhabitants, Melilla has one of Europe's only two land borders with Africa, along with Ceuta, another Spanish territory to the west.
Travelling to Melilla via Turkey, Algeria and Morocco aided by human-traffickers, "the children have been exposed to suffering, hunger and violence," said Save the Children's director for Spain, Andres Conde.
The organisation, which has observers at the scene, said Moroccan police had occasionally closed the border with Melilla to Syrians while some families were getting separated on either side of the frontier.
"It is unacceptable that such situations are occurring at the border of Europe," Conde said.
Thousands of civilians fleeing Syria's civil war have headed to Melilla in recent years. Many of them say they want to pass through Spain and head to northern Europe, according to aid groups.
Of the hundreds of thousands of refugees from Syria and elsewhere arriving in Europe, Spain has agreed to take in 14,931 in addition to 2,749 whom it accepted in July