It happened in the 8300 block of State Road at about 3:15 p.m. Monday.
Police say a motorcyclist was apparently trying to avoid a tractor trailer that was making a turn when he struck a car.
The motorcycle driver, a man in his 20s, and his female passenger, 23, were both rushed to Aria Torresdale in critical condition. The driver was pronounced dead a short time later.
The 72-year-old driver of the car was taken to Hahnemann University hospital with a leg injury.
An investigation is underway.