The crash happened around 9 pm in the area of Shields and Sierra Vista avenues.
The California Highway Patrol initially responded to the scene, but Fresno police have taken over the investigation.
Fresno police say when officers arrived, they found a man in his 30s with a broken arm near his motorcycle.
While being treated, officials say the man believed he had a person on the road.
Officers later found a woman in her 40s who was taken to the hospital, but she later died from her injuries.
Stay with Action News for the latest updates on this developing story.