The crash happened on the R290 at Dunamurry, Ballygawley, at about 19:30 on Monday.
The woman was pronounced dead at the scene and her remains have been taken Sligo University Hospital where a post-mortem examination is due to take place.
The driver of the second car was also taken to hospital for treatment of injuries which are not life-threatening.
The N290 between Ballygawley and Ballintogher remains closed for a technical examination and diversions are in place.
Gardaí have appealed for anyone with http://berdasarkanapa.com/ information or dashcam footage from the collision to contact them.