Police were called to the scene of the smash, between the Strines junction and Ladybower, at 9.50pm last night following reports that five cars had been involved in two collisions.
The first involved a black BMW, a white Honda Civic and a silver Honda Civic.
The BMW driver, from Sheffield, was rushed to the Northern General Hospital but could not be saved.
His three passengers were injured, two of them seriously.
They remain in hospital this morning.
The white Honda driver - a man from Cheshire - was pronounced dead at the scene while his passenger suffered serious injuries and was taken to hospital in Sheffield, where he remains.
A man driving the silver Honda was also seriously injured and remains in hospital.
A Vauxhall Corsa and a Volkswagen Polo on the road at the time also collided following the smash, Those drivers were not injured.
A Derbyshire Police spokeswoman said: “The road was closed while emergency services worked to extract victims and clear debris. It was re-opened at 7am today.
“Police want to speak to anyone who saw the BMW driving in the area prior to the collision.”
The BMW is reported to have been seen driving ‘erratically’ before the crash.
Anyone with information should call Derbyshire Police on 101, quoting incident number 732 of May 15.