The crash happened at about 10:22 p.m. near the intersection of Route 53 and Dollar Tree Lane, police said.
A man, 58, was driving a Volvo semi tractor-trailer eastbound on Dollar Tree Lane when he attempted a left turn onto northbound Route 53, police said.
At the same time, a 40-year-old man driving a Dodge Dart was traveling south on Route 53.
The Dodge crashed into the trailer, and police said it ended beneath it.
The driver of the Dodge died at the scene. Police said he was from Wilmington. His identity has yet to be released.
A 2-year-old boy was in a car seat on the back seat of the Dodge. The boy was taken to an area hospital in serious condition.
Anyone with information regarding the crash is urged to call police.
No other information regarding the crash was available.