Gloucestershire Police said it happened at about 05:25 GMT on the southbound carriageway, just north of junction 13.
The 21-year-old driver of a BMW was killed, a spokesman said. The driver of the articulated lorry was unharmed.
A police spokesman said the southbound carriageway of the motorway remained closed between junctions 12 and 13 until after 13:00 GMT.
Long queues of traffic were reported on surrounding roads as drivers followed diversions.
The coroner and the victim's next of kin have been informed, but formal identification of the man who was killed has not yet been carried out, police said.
A man from Gloucester has been killed in a crash involving a lorry and a car on the M5 near Stroud.