The crashes took place within a mile-and-a-half-stretch in between the B4047 and the A415 at Witney, as per South Central Ambulance Service.
4 other individuals were taken to hospital – one with deadly injuries.
About 15 people were dealt with at the scene, the ambulance service stated.
Another of those taken to healthcare facility had suffered severe injuries, while the other 2 had small injuries.
Thames Valley Police verified the crash through its TVP Roads Policing account.
It stated: “The A40, Witney is closed following a multi-vehicle crash. Emergency services are on scene and drivers are advised to avoid the area.”
Mother-of-two Ami Gaston, from Carterton, was in the automobile with her partner when she saw the first car crash about half a mile from the Witney exit, obstructing the right lane.
“A guy on his own had skidded and crashed into middle barrier,” she stated.
“My partner was driving – we had to swerve out of the right lane to avoid striking him.”
She said heavy fog indicated the scenario was “really” harmful, as it was difficult to see other vehicles until you were “on top of it”.
One lane of the westbound carriageway of the A40 was resumed and the 2nd lane is due to resume as soon as repairs have been finished to the central reservation, Thames Valley Police stated.
The eastbound carriageway was due to remain closed till about 19:15 to enable the last automobiles associated with the crashes to be recovered and the road surface area to be cleared of particles, the force included.
All automobiles not associated with the collision have been released from the location.
Oxfordshire County Council stated the roadway had actually been gritted overnight.