The male driver, 54, and 16 passengers suffered injuries including broken bones, cuts and bruises in the horror collision.
Thick fog made access to the scene at Junction 7, near Thame, Oxfordshire more difficult to access, South Central Ambulance Service (SCAS) revealed.
Shocking pictures show the destruction after the vehicle smashed into the road near Milton Common and come off the sliproad.
Members of the emergency services work at the scene of a multiple car collision on a main road in heavy fog near Witney
One passenger onboard the Oxford Bus Company coach – among holidaymakers returning from London’s Heathrow Airport – hailed the coach driver a “hero”.
The university student told The Mirror: “Someone shouted that they could smell fuel so we all tried to clamber out which meant clambering over the seats.
“He wouldn’t leave the bus until all the passengers were off”
“At one point we were actually walking on the overhead luggage racks.
“The bus driver was at what was the front of the bus and helped us all out even though he was obviously bleeding pretty heavily and some of his blood was on the floor.
“He wouldn’t leave the bus until all the passengers were off.”
Six ambulances took the injured passengers to John Radcliffe Hospital in Oxford.
The road will be shut for several hours, Thames Valley Police said.
Emergency services have now flipped the coach upright.
The Oxford Bus Company coach smash took place at 2.45am this morning.
It crashed just 20 miles away from where a woman was killed yesterday in a 20-car pile-up on the A40 near Witney, Oxfordshire.
Drivers have been warned of the fog and ice putting motorists at risk over the New Year weekend.
The poor weather conditions could prove “lethal” and Brits should head out onto the roads with “extreme caution”, the AA said.
Spokesman Ian Crowder said on Thursday: “We have got the worst possible conditions really, of fog and icy roads, and that can be lethal.
“I think the message is extreme caution and to prepare for the worst and make sure all windows are clear.”
Visibility could be as low as 100 yards with icy conditions on the road amid the “yellow” fog warning, Met meteorologist Emma Sillitoe warned.
An SCAS spokesman said: “South Central Ambulance Service declared this a major incident due to the number of patients involved and attended the scene with our colleagues from Thames Valley Police and Oxfordshire Fire and Rescue Service.
“There was thick fog in the area at the time of the accident which also presented challenges to the emergency services getting to the scene.”