The man was seriously hurt when his HGV ended up off the northbound carriageway of the M6 between the Marus Bridge and Orrell junctions on Friday morning.
He was taken to hospital but sadly lost his fight for life.
His family is being supported by specially-trained officers and police are now appealing for witnesses or information about the incident.
The entire northbound carriageway had to be shut for several hours while police and the ambulance services attended the scene.
All lanes of the motorway have since re-opened. Motorists travelling north for much of Friday had to use a diversion.
Anyone with information is asked to contact Greater Manchester Police on 101, quoting reference number 318 for 22/03/2019 or email PC Mark Milner at [email protected]