A lorry and seven cars were involved in the accident on the A34 at Hinksey Hill, Oxford, at about 19:30 BST on Thursday.
The child and a 31-year-old woman were taken to Oxford's John Radcliffe Hospital, where they were described as being in a "critical" condition.
Police have now said the girl died on Saturday.
The woman remains in hospital where she is receiving treatment.
They were travelling northbound in one of the cars when the accident happened, and the carriageway was closed for almost 10 hours.
A 58-year-old man was arrested on suspicion of causing serious injury by dangerous driving.
A three-year-old girl has died in hospital following an eight-vehicle crash on a dual carriageway.