At around 8.35am on Tuesday morning, officers were called to a report of a road crash involving a Mini and a Seat Ibiza on the A6091 at the B6539 junction in Melrose.
Emergency services attended and the 30-year-old driver of the Seat was pronounced dead at the scene.
His next of kin has been informed.
The 57-year-old female driver of the Mini was taken by air ambulance to the Royal Infirmary of Edinburgh where she is being treated for her injuries.
Hospital staff describe her condition as serious.
Sergeant Kosmas Papakyriakou, of Police Scotland’s Road Policing Unit, said: “Our thoughts are with the family and friends of the man who has died.
“Enquiries are ongoing to establish the exact circumstances surrounding this crash and I would appeal to anyone who witnessed this crash or who has any information that may assist our ongoing investigation.
“We are particularly keen to speak to the driver of a red van who was in the area around the time of the incident.
“I would also appeal to anyone driving on the road around the time of the crash who has dash-cam footage to contact us.
"Information can be passed through 101 quoting reference number 0603 of 1 February.”
Following the crash, the road was closed until late afternoon as officers inspected and cleared up the scene, with diversions in place for drivers.