The woman, the driver of the car, was pronounced dead at the scene near Shifnal after paramedics found her in a serious condition just after 9am.
The crash led to severe delays for drivers in the area, with the A5 shut between Crackley Bank and Pickmere Island, where the A5 crosses the A41 on the Shropshire/Staffordshire border.
The road remains closed at this time.
West Midlands Ambulance Service spokesman Jamie Arrowsmith said: “On arrival we discovered the driver of the car, a woman, in a serious condition.
“She was quickly rescued from the vehicle by ambulance staff who immediately began administering advanced life support.
“However, despite their best efforts it unfortunately became apparent that nothing could be done to save her and she was confirmed dead at the scene.
“The driver of the lorry, a man, was assessed but uninjured in the incident.”
The Midlands Air Ambulance was called to the scene, as well as an ambulance and a paramedic officer.
Diversions were in place and motorists were advised to avoid the area.
A West Mercia Police spokesman said: "At 9.10am this morning police responded to a report of a collision on the A5 near Burlington, Shifnal, involving two vehicles. A section of the road is closed while emergency services deal with the incident."
Enquiries are ongoing and police are appealing for witnesses, including any motorists on the road this morning with dash cam footage.
Anyone with information should contact Pc Andy Burrell on 101 ext 5785.