The accident happened around 11:30 a.m. in the westbound lanes of the highway near South Pleasantview Road.
Officials say the driver of a Chevy lost control and the vehicle rolled over several times. A 44-year-old woman inside the car was ejected and later pronounced dead.
Police say the 33-year-old male driver was transported to Pottstown Hospital. There is no word on the extent of his injuries.
The westbound lanes of Route 422 were shut down for about 4 1/2 hours but all lanes have since reopened.
The cause of the accident remains under investigation.