The A1 heading southbound is closed between junction 47 and 48 near Boroughbridge.
The crash happened at 7.48am this morning (June 12) and involved a single vehicle.
North Yorkshire Police said: "The driver and passengers of the vehicle are believed to have serious, but not life threatening, injuries."
Anyone travelling in the area is urged to avoid the A1 due to heavy congestion.
The road reopened at around 1.30pm.
Police also asked anyone who witnessed the crash to contact police on 101, passing on information to the force control room.
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