Highways England said the eastbound side of the M62 is likely to remain closed between junctions 18 and 19 into the evening after the collision.
The incident happened at 12.45pm near Heywood, and traffic officers are currently working with the emergency services at the scene.
The eastbound carriageway has been affected by significant diesel spills and the central reservation barrier is badly damaged.
Lane 3 on the westbound carriageway is also currently closed.
A signed diversion is in place at the stretch of motorway and drivers are being advised to check the latest travel conditions before setting out on journeys and to use alternative routes.