It is understood the heads of former Labor prime ministers Paul Keating and Kevin Rudd were stolen.
The name plates of the remaining statues were covered in spray paint, police said.
The City of Ballarat took to social media to condemn the attack.
“The Prime Ministers Avenue was vandalised with several statues extensively damaged,” the city said.
“This type of senseless damage is completely unacceptable. It is not only extremely costly to our ratepayers and will divert money away from critical Council services, but it detracts from Ballarat as a city.”
Police are keen to speak to anyone who saw suspicious behaviour in the area.