The collision happened on the A82 between Glasgow and Fort William, near the Falls of Falloch, at around 5.15pm yesterday.
Police said the crash involved a blue VW Golf travelling south and a blue Mercedes going the other way.
An 86-year-old woman who was in the front seat of the Mercedes suffered fatal injuries in the crash. She will not be identified until her family members have been told.
Officers said the other people in the car were seriously injured, but they have not yet said how many were hurt or what their ages are.
Police are urging anyone who may have information surrounding the crash to contact the trunk road policing group at Stirling on 101.