Police have confirmed seven people were killed in the 34-car pile-up on the M5 near Taunton.
The accident happened at around 8.15pm on Friday night. Police believe 51 people have been hurt, some with "life-changing" injuries.
Reports from other news outlets suggest that there may be as many as 16 fatalities, with the death toll expected to rise.
These reports remain unconfirmed.
Footage has emerged of burning vehicles and firefighters battling to control the blaze. Motorists were trapped while their cars were ablaze. One police officer described the scene as "one massive fireball."
Cars and lorries were engulfed in flames following the accident, ignited by the large amounts of flammable fuel from the vehicles.
Assistant Chief Constable Anthony Bangham of Somerset and Avon Police described the devastating crash as "very, very challenging" for emergency workers.
"On arrival crews were faced with literally one massive fireball. Most vehicles were well alight and most continued to burn for a considerable time.
"This made it very difficult to search the vehicles. Some of them have been burned to the ground."
The horrific crash, which involved at least four lorries, was attended by fifteen fire engines and is was described by one emergency person on the scene as the "worst road accident in 20 years".
Police said the death toll was expected to rise.
"We do believe there could be more deaths," said Bangham.
"Our thoughts are with those who may have lost loved ones as a result of last night's collision."
Of the casualties, 25 were taken to Yeovil District Hospital while 17 of the more seriously injured were taken to Musgrove Park Hospital in Taunton. Nine others were taken to a temporary holding unit set up by the ambulance service.
A large-scale operation is now underway to check there are no other casualties and work will soon begin on repairing the carriageway and removing the vehicles, which will all have to be forensically examined.
Chief Constable Colin Port, who visited both the site and casualty bureau overnight, also gave his condolences to those who had lost loved ones.
"I would like to say a huge thank you to officers from all the emergency services who have had to deal with this very difficult and traumatic incident," he said.
Transport secretary Justine Greening also expressed sympathy with the families of those affected by the tragedy and thanked rescue workers and emergency staff who worked throughout the night to help the injured.