The car crash, which occurred on the new Sheppey crossing bridge on the A249 in Kent early Thursday, reportedly went on for 10 minutes as cars continuously collided with each other.
There are reports of six serious injuries and 200 minor injuries, police said, and five people had to be freed from their vehicles by firefighters using hydraulic cutting equipment.
The scene on the bridge was a mass of tangled cars, lorries and even a car transporter as one witness said "all you could hear was cars crashing".
South East Coast Ambulance Service said it was dealing with a major incident with 30 ambulances and cars at the scene. There were no fatalities.
The accident, which happened at 7.15am, is thought to have occurred in thick fog, with some witnesses saying that visibility was down to 20 yards in places and some motorists were driving carelessly prior to the pile-up.
A Kent Police spokeswoman said visibility was a problem over the bridge, but it was not clear whether that caused the pile-up. The £100m four-lane crossing opened in 2006.
Witness Martin Stammers, 45, from Minster, said: "It's horrific. I've never seen anything like it in my life."
"All you could hear was cars crashing. We got out of our car and it was eerily quiet, with visibility down to just 20 yards."
Seven fire engines were also at the scene and motorists were warned to avoid the crossing, which connects the Isle of Sheppey with mainland Kent.
NTJ/NJF