The A666 between Bolton and Salford was closed for more than four hours after a car collided with a wall.
A man, understood to be in his early 50s, suffered serious injuries in the crash and has been taken to hospital.
Emergency services were called to the scene, close to the Unity Brook Inn in Kearsley, just after 11.30am on Tuesday following reports of a collision.
It is not clear at this stage exactly what happened, but a spokesman for GMP confirmed there was just one vehicle involved in the incident.
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Specialist firefighters helped to free the man from the vehicle, before he was treated by ambulance crews and taken to hospital.
He is understood to have suffered serious injuries.
The A666 remained closed into Tuesday afternoon, affecting traffic between Kearsley and Clifton.
It was reopened at around 4pm.
TfGM tweeted: "Due to a police incident, the A666 Manchester Road in Kearsley is currently closed in both directions near the Unity Brook Inn
"Find an alternate route."
A spokesman for the North West Ambulance Service said: "We were called at 11.31am to reports of an RTC.
"A man in his early 50s was taken to hospital with serious injuries."
