A dark blue 4x4 and an orange Fiat were involved in a head on collision just after 7.30pm last night.
Firefighters from Bracknell, Wokingham and Crowthorne fire stations were called to the incident, which took place between the Nine Mile Ride and Hanworth roundabouts.
The woman driver of the Fiat was taken to the Royal Berkshire Hospital with suspected broken legs, while the male passenger was also taken to hospital with suspected serious injuries.
Firefighters had to cut all the doors and the roof off the car to free the couple, whilst the man driving the 4x4 was also taken to hospital as a precaution.
Another person was taken to hospital as a precaution for fear of spinal injuries.
Police and four ambulance crews attended the scene.
James Keating-Wilkes, from South Central Ambulance, said paramedics treated a further three people at the scene but they did not need to go to hospital.
The road was closed for about two hours but reopened later last night. Fire crews left the scene just before 9.30pm.