A female motorist died as the result of a collision on the A6 Chapel-en-le-Frith bypass, which occurred at around 2.25pm.
Police say the woman, aged in her late 70s and believed to be from the Stockport area, was the driver of a silver Fiat Panda which was in collision with a blue Vauxhall Zafira.
The driver of the Vauxhall, a man in his 50s, sustained serious injuries and is being treated in hospital.
The road was closed for around five hours while emergency services attended the scene.
Later the same day, at around 9pm, a grey Citroen C3 carrying three people left the carriageway, went through a metal railing and collided with a tree, on Sheffield Road, Chesterfield, close to the Sandpiper Hotel.
The driver, a 35-year-old woman, suffered fatal injuries and was pronounced dead at the scene.
Two male passengers - one of whom suffered serious injuries - were taken to Sheffield’s Northern General Hospital.
Witnesses to either collision are asked to contact Derbyshire Constabulary on 101.
Information relating to the Chapel collision should be passed to DC 919 Glynn, quoting incident number 372 05/05/14.