Members of the public performed CPR on the man, believed to be in his 20s, after the crash happened in Lichfield on Wednesday evening, but he could not be saved.
The collision involved a white Audi and a black Yamaha motorbike and happened at the junction of the A5192 Eastern Avenue and Grange Lane just before 7.30pm.
Paramedics arrived to find bystanders already performing "excellent" life support and an air ambulance was also sent but the man was pronounced dead at the scene.
Staffordshire Police is now appealing for witnesses following the crash.
A spokesman for Staffordshire Police said: "Police are appealing for witnesses after a motorcyclist died in a road traffic collision in Lichfield.
"Officers were called the junction of Grange Lane and Eastern Avenue at 7:30pm on Wednesday to a report of a collision involving a white Audi and a black Yamaha motorcycle.
"Sadly, despite the best efforts of paramedics, a man in his 20s was pronounced dead at the scene.
"The man’s next of kin have been informed and his family are being supported by specially-trained officers."
West Midlands Ambulance Service spokeswoman Claire Brown said: “When ambulance staff arrived at the scene of the collision, they found bystanders performing excellent CPR on a man, the motorcyclist, who was in a critical condition.
“The team of ambulance staff quickly took over treatment and commenced advanced life support.
"Tragically, despite the very best efforts of WMAS and bystanders, they were unable to save the man’s life and he was confirmed deceased on scene a short time later.”
Anyone who witnessed the crash, or has any dash-cam footage, is asked to call Staffordshire Police on 101, quoting incident number 668 of June 16.