A woman has died following a major crash involving around 20 vehicles on the A40 near Witney in Oxfordshire, Thames Valley Police said.
Several people are also believed to have been injured.
The A40 has been closed in both directions after multiple vehicles crashed into each other near Witney in Oxfordshire at around 8.25am, police said.
Images showed the mangled wreckage of several of the cars involved, with debris strewn across the road.
Driver Ben Starkey told the Oxford Mail: “There were two vehicles facing me and on further inspection I could see two cars had gone into the back of each other.
“There was a vehicle screwed up with dents all over and a lady on the floor in a serious condition. There was further destruction behind me.”
The incident is likely to cause major disruption for many people travelling across the country following the Christmas break, as the road connects London to Wales.
A Thames Valley Police spokesman said: “Thames Valley Police officers were called today at about 8.25am following reports of a collision involving multiple vehicles on the A40, Witney.
“Officers are at the scene along with the fire and rescue services. A number of people are believed to have been injured.
“Road closures are currently in place, and drivers are advised to avoid the area.”