Police said a car had gone through the central reservation after colliding with a lorry and then crashed into traffic on the westbound carriageway.
The car hit two more lorries and another car at junction 21 at Milnrow just after 09:30 BST.
Police said the dead man was yet to be identified. A man and woman also suffered serious injuries.
The pair, who were travelling in one of the cars, were flown to Royal Oldham Hospital by air ambulance. Their conditions are described as not life threatening.
Eight other people suffered minor injuries but did not require hospital treatment, police said.
The crash has closed the M62 in both directions and another minor accident just after 11:00 BST near Huddersfield also caused further tailbacks into Yorkshire.
PC Ed Lister from Greater Manchester Police said: "Our officers are doing all we can to identify this man as quickly as possible so we can speak with his family, and also to deal with the other injured people and damaged vehicles at the scene.
"There are considerable traffic tailbacks following this collision and we are advising people wherever possible to avoid this area and use another route."
A man has died and 10 people have been injured in a multi-vehicle accident on the M62 near Rochdale.