In the second crash a woman died in a head-on collision in Narre Warren North at Heatherton Road and Fairmont Court about 2.30pm.
A 43-year-old Narre Warren man was arrested and is assisting police with their enquiries.
In the third incident, a 22-year-old Swan Hill woman was killed after she lost control of her car as she travelled around a bend in the state’s north-east just after 4pm on Friday.
The car crossed onto the wrong side of Pental Island Road at Pental Island, travelling down a grass slope before crashing into a tree.
Nobody else was in the car and the woman died at the scene.
In the fourth crash, a 26-year-old motorcyclist was killed in a collision with a truck in Oakleigh.
Police say a B-double truck travelling south on Warrigal Road had just passed the intersection of North Road about 6.30pm, when the motorcyclist attempted to overtake the truck in the left lane.
As the lane ended the truck and motorcycle collided, killing the male rider.
The uninjured truck driver, a 61-year-old Wyndham Vale man, has been assisting police with their investigation. In the fifth deadly crash a motorcyclist was killed in Keilor East about 11.40pm.
Investigators believe the male rider may have lost control turning onto the Calder Freeway near Keilor Park Drive. The man, who is yet to be formally identified, died at the scene.