Emergency services were called at 7pm today after the crash at the intersection of the Hume Highway and Worth Street in Greenacre.
NSW Ambulance paramedics treated the rider and pillion passenger of the motorbike but both died at the scene, police said.
The driver of the car was rushed to Westmead Hospital in a critical condition.
Worth Street is closed between the Hume Highway and Muir Road and diversions are in place.
