Bedfordshire Police said a Renault articulated lorry was on the M1 southbound at around 3.30am, when it was in a crash with two other lorries.
The driver of the Renault lorry, who is believed to be a 62-year-old man from Skegness in Lincolnshire, died.
He has not been named by police, and family liaison officers are supporting his family.
Police have appealed for anyone who witnessed the crash, which happened on the M1 southbound just north of junction 13 and forced a stretch of the busy motorway to be closed in both directions, to contact them.
An investigation is under way and the road is now open, a Bedfordshire Police spokeswoman said.
An inquest will be opened and adjourned in due course, after which the victim will be named.
Anyone with information should contact Pc Bob Hauxwell, in the Collision Investigation Unit, on 01438 757500, text to 07786 200011 or telephone Crimestoppers on 0800 555 111.