It happened just before 7 a.m. on Tulare Street and R Street.
Fresno police say the driver of the vehicle stayed at the scene and was cooperative with officers.
Traffic in the area will be closed until 9 a.m. as officers continue to investigate.
The closure has traffic backed up and has caused slowdowns on Highway 41.
Officials are encouraging drivers to avoid the area and to use the O Street off-ramp if they plan on going downtown.
This is a confirmed fatal collision. The area is expected to be closed until after 9am. Consider using the O Street off ramp to access down town.— Fresno Police (@FresnoPolice) March 11, 2020