A lorry transporting a mobile home has crashed through the central reservation on the M62 hitting a car travelling in the opposite direction.
The crash blocked the motorway in both directions at Ouse Bridge, near Goole, at about 09:30 BST, with the eastbound carriageway remaining closed.
Commuter Steve White said the home had "come off the back of the lorry and was stopped from careering off the side of the bridge by a barrier".
Police are yet to confirm any injuries.
Humberside Police said the lorry was travelling westbound when it went through the central reservation and smashed into a car, which was heading eastbound.
The closure to the eastbound carriageway could extend overnight and even disrupt Wednesday's rush hour traffic, a force spokesperson said.
Emergency services including the air ambulance have been at the scene of the crash, described as "serious" by police.
Mr White, 60, from Leeds, was heading to work in Howden when he saw vehicles braking in front of him.
He said he stopped about 200 yards from the scene and described how the mobile home had "come off the back of the lorry and was stopped from careering off the side of the bridge by a barrier".
"It must have only just happened when I saw the cars' brake lights in front."
Highways England said it was working to free drivers who had been stuck in the tailbacks for several hours.
It said traffic was being redirected and motorists should remain in their vehicles.