Police confirmed a seven-year-old girl died at the scene after a 4WD with seven children inside rolled at Parwan, west of Melbourne, shortly before 4pm on Tuesday.
The eight-seater came to a stop on grass between the road and a paddock.
Paramedics rushed to the scene and airlifted a critically injured 11-year-old boy to hospital, who died overnight.
Five other children were taken to hospital with non-life-threatening injuries.
The driver, a 34-year-old woman, was taken to hospital for observation.
Detective Acting Sergeant Tony Gentile described the scene as "quite hectic" with several people witnessing the crash.
"There were people everywhere," he told reporters at the scene.
"This is just a really sad set of circumstances."
Specialist ambulance resources remained at the crash scene, near the Nerowie and Parwan-Exford roads intersection, into the evening.
Among them were two helicopter crews, two mobile intensive care ambulance paramedic crews and five advanced life support paramedic crews.
Detectives are investigating the circumstances surrounding the crash, about 58km from Melbourne's CBD.
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