Police are appealing for witnesses following the incident, which happened just south of the Cousland junction at around 4.20pm on Friday.
A blue Ford Fiesta, travelling southbound, collided with a white Land Rover Discovery Sport that was travelling northbound.
The 46-year-old driver of the Ford died on impact, and her next of kin has now been informed.
The 62-year-old driver of the Land Rover was taken to Edinburgh Royal Infirmary, where he remains in a serious condition.
The road is closed from the Cousland junction to north of Pathhead, and local diversions are in place. It is expected to remain closed for some time while collision investigations are carried out.
Anyone with information on the crash is asked to call police on 101 or through Crimestoppers on 0800 555 111.