One of the early hours collisions in Holymoorside saw an 18-year-old man arrested and a young woman hospitalised with serious injuries after a car collided with a tree.
Another crash caused the closure of Cromford Road at Langley Mill between the A610 and Plumptre Road.
However a further collision is also understood to have happened at Clay Cross.
Derbyshire Roads Policing Unit tweeted: “Unfortunately a terrible and tragic night across the roads of Derbyshire.
"Three serious collisions in Clay Cross, Holymoorside and Langley Mill.
"Further details will follow in coming days. Some of our night shift only just getting home.”