The two casualties were taken to the Royal Berkshire Hospital after two vans and three cars were in collision shortly before 1.30pm close to the Citreon garage.
Police closed the road for nearly an hour to clear the wreckage, with the incident causing long tailbacks in the town centre and Rose Kiln Lane. Crews from Caversham Road fire station were called there but did not need to free anyone from the wreckage.
A motorist said: "I could see people being taken away on stretchers.
"There was a van involved, it is smashed to pieces. The other vehicles looked like family cars.
"Traffic is also a bit slow northbound because of rubber-neckers."