Police have shut Caton Road (A683) both ways between M6 junction J34 (Lancaster) and the Denny Beck layby near New Parkside Caravan Park.
Drivers can still access the motorway via the Bay Gateway, but it is affecting travel between Lancaster and Caton.
The crash happened at around 8.40am and police say the road is likely to remain closed for some time.
Details on casualties has not been released at this stage, but police are advising motorists to avoid the area whilst accident investigation work takes place.
Lancaster Area Police posting on Facebook said: "Please note that Caton Road (A683) is closed due to a RTC between the M6/Bay Gateway and the Denny Beck layby.
"Please avoid as this will be closed for some time."
Lancashire Police and North West Ambulance Service has been approached for further details.
More to follow...