The incident happened at around 4:20 pm this afternoon on the N6, about 3 kilometres from Craughwell, on the Oranmore to Craughwell road.
The woman, who is in her fifties was the only occupant in her car when she collided with another vehicle.
She was pronounced dead at the scene.
The three occupants of the second vehicle were injured and taken to University Hospital Galway. Their injuries are believed to be non-life threatening.
Local diversions are in place.
Gardaí are appealing for witnesses to contact them at Oranmore Garda Station on 091-388030 or any Garda Station.