According to AA Traffic, the collision happened in the northbound lanes of travel after a car overturned and then was struck by two other vehicles.
The collision occurred between the junctions 9 A34 (Bicester) and 8 (Oxford).
The road will be closed for a considerable period of time.
Please find an alternative route.
Emergency services personnel with the Oxfordshire Fire and Rescue Service and the South Central Ambulance Service have responded to the crash.