The A63 westbound is now closed between junctions with the A15 near Hull and A1034 at South Cave following the crash.
Highways England said a closure will remain in place for a number of hours.
A vehicle collided with a bridge and debris scattered across the carriageway.
A spokesperson for Highways England said: "Due to the nature of this incident it is anticipated that the closure will remain in place for a number of hours.
"This incident is led by Humberside Police with assistance from Highways England. "