It happened around midnight Thursday on Route 55 near the Garden Road exit.
Police said two cars collided in the northbound lanes.
Officials said five children were thrown from a minivan. One child died.
The drivers of both vehicles were taken to an area hospital, but are expected to be OK, officials said.
The investigation shut down the highway for hours. The northbound side remained closed until 6 a.m.
The cause of the crash is still under investigation.