The incident happened shortly after 19:00 on the A9 Inverness to Thurso road, on the outskirts of Thurso.
The driver of a Ford Fiesta was pronounced dead at the scene. The female driver of a Nissan Qashqai was unhurt.
The road was closed in both directions at the crash site for a police investigation.
Sgt Donnie MacKinnon, from the Road Policing Unit, said: "Tragically this collision has resulted in the driver of the Fiesta sustaining fatal injuries and we are currently trying to establish the full circumstances surrounding this incident.
"Anyone who was on the A9 just outside Thurso at around 7pm on Thursday evening and witnessed what happened should contact police immediately."
A male driver has died after he was involved in a two-car collision in the Highlands.