The A59 Longton bypass was shut both ways between Hutton and Walmer Bridge after a vehicle, understood to be a lorry, struck a bridge in New Longton.
Preston Police said in a statement: "We are currently dealing with a road traffic collision on Chapel Park Road where a vehicle has collided into the bridge causing damage.
"As a result we have had to close the A59 between the junctions of the Anchor roundabout at Hutton and Gill Lane, Walmer Bridge for safety reasons. Please avoid the area and find alternative routes for time being."
One driver said: "Chapel Park Road has been blocked off at both ends, while Chapel Lane is also closed and people are being stopped from accessing the bypass."