The motorway had been closed in both directions from 3.30am, between junctions 20 (M56, Lymm) and 19 (Knutsford), after an accident involving two lorries, a van and a car.
But the northbound carriageway reopened at around 7.30am after investigation work was completed at the crash scene.
But the southbound carriageway remains closed for repairs after debris and diesel spilled across three of its lanes.
Police say one driver has been taken to hospital. North West Ambulance Service has been approached for further details on the casualty.
Highways say the southbound carriageway will remain closed until around 11am, whilst the diesel spillage is cleaned up.
If you need to travel southbound, you will have to go eastbound on the M56 then southbound on the A556, following the Hollow Triangle symbol, say Highways England.