A Volvo articulated lorry, a Mercedes Sprinter van and a Honda Civic collided at the Keir roundabout south of Dunblane.
Emergency services were called to the scene at around 6.25pm on Thursday.
The 25-year-old driver in the Honda Civic died as a result of the crash.
The 26-year-old female passenger in the Honda Civic was seriously injured and remains in hospital. The 41-year-old driver of the Mercedes Sprinter was also injured and remains in hospital.
An air ambulance landed on the road during the emergency services response to the crash.
Fire crews from Dunblane, Doune, Bridge of Allan and Stirling also assisted with the rescue operation.
Police have confirmed the collision resulted in one fatality and closed the A9 in both directions until just after midnight.
A report will be submitted to the Procurator Fiscal.
Sergeant Michael Montague of Forth Valley Road Policing Unit said: “A man has died in this collision and a passenger and one other driver seriously injured and we are keen to hear from anyone who witnessed the collision.
“Anyone with information that can assist us with our ongoing inquiries is asked to contact officers via 101.”