The cyclist – a 59-year-old Alphington man – suffered head injuries and was taken to the Royal Melbourne Hospital where he remained in a critical condition on Sunday evening.
The woman driving the car was not injured and assisted police at the scene.
Police with Greensborough Highway Patrol closed the intersection of Banksia Street and Lower Heidelberg Road for a short time, but it has since been reopened to traffic.
Police would like to speak to a second driver, not involved in the crash, who stopped to render assistance but left before police arrived.
Anyone who may have witnessed the collision is urged to contact Crime Stoppers on 1800 333 000.