The quake hit about 1.55am, Geoscience Australia said.
More than 5700 residents across the state have reported feeling the tremors, with thousands of those in Melbourne CBD and some as far north as Bendigo.
There have been no injuries or damage so far, Victoria SES said.
It was the second earthquake to rock Leongatha in days.
Another magnitude 4.3 quake was felt about 12.49am on Friday.