Two young children have died despite the heroic efforts of motorists following a crash on a major highway in Sydney’s southwest.

The pair, aged one and five, were sitting in a pram when they were hit by a car in Cabramatta on Wednesday afternoon.

Acting Superintendent Timothy Calman praised the efforts of bystanders, telling reporters a number of motorists stopped and worked together to lift the vehicle in order to free one of the children trapped underneath.

“It’s probably one of the most confronting scenes that police come across, dealing with young children,” Calman said.

“It’s tragic circumstances for the family.

“The community involved here this afternoon was, I can only say, phenomenal.”

Two children have died after a crash on Cumberland Highway.Two children have died after a crash on Cumberland Highway. Credit: 7NEWS Paramedics and other emergency personnel can be seen treating patients.Paramedics and other emergency personnel can be seen treating patients. Credit: 7NEWS

Bystanders also helped perform CPR on the children and their mother.

Emergency services were initially called to the intersection of Joseph and Gilbert Sts about 3.15pm on Wednesday.

The children were treated before being rushed to The Children’s Hospital at Westmead in a critical condition, where they later died.

The 33-year-old mother was treated for minor injuries at the scene.

The driver, a 56-year-old man, was uninjured and was arrested before being taken to hospital for mandatory testing.

Calman said the driver was not known to police nor the victims.

Police said the two children were in the pram when they were hit. Police said the two children were in the pram when they were hit. Credit: 7NEWS

A crime scene has been established and investigations are underway.

All southbound lanes of the Cumberland Highway have been closed between John St and Cabramatta Rd West.