Police said the tree fell onto two passing cars, injuring a man and a woman travelling separately, with both casualties taken to Royal Preston Hospital with head injuries.
The injured man was rescued from his crushed car by firefighters, along with his unharmed passenger, after the pair were left trapped in their seats when the tree came crashing down on them.
He was taken to hospital by ambulance, along with the female casualty, but there injuries are not thought to be serious.
Wigan Road remains shut between Shady Lane and the A6 Lostock Lane whilst the tree is cut up and removed.
Lancashire Police said it expects the road to remain closed “for sometime” and is advising drivers to avoid the area until further notice.
Those heading towards the A6 at Bamber Bridge are being diverted down Lydiate Lane and along Stanifield Lane in Farington, back to Lostock Lane and the A6.
A police spokesman said: “We were called around 7.35am today (Thursday, April 7) to a report a tree had fallen on two cars in Wigan Road, Bamber Bridge.
“Two people were initially trapped in one vehicle and later freed by the fire service. No injuries were reported.
“A woman driving another vehicle suffered a minor head injury during the incident.
“A road closure is in place while the tree is removed.”