Police believe the car had been travelling northbound when it left the carriageway on the approach to Stones Bank Road.
The driver - a man in his 20s, from Brierfield - was taken to hospital with serious injuries to his head, chest and hip.
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His injuries are not thought to be life-threatening.
Sgt Craig Salmon, of East Tactical Operations, said: "This incident has resulted in a man suffering some quite serious injuries and my thoughts are with him and his family at this time.
"We are now working to establish a fuller picture of what occurred.
"I would ask any witnesses or anybody with CCTV or dashcam footage which could assist our investigation to get in contact with police as soon as possible."
No other vehicles are thought to have been involved in the collision.
The road was closed for approximately seven hours while emergency services made the scene safe.
A spokesman for Lancashire Fire and Rescue Service said: "Two fire engines from Darwen attended a road traffic collision on Stones Bank Road in Darwen.
"Firefighters used one breathing apparatus and one hose reel at this incident.
"They were in attendance for one and a half hours."
Anyone with information can email [email protected] or call 101, quoting log number 0063 of September 15.
You can also report any information online at doitonline.lancashire.police.uk.
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