The joint operation by Victoria Police and the Therapeutic Goods Association has disrupted the supply of vapes worth an estimated $A15 million ($NZ16.35m) on the streets.
"While the investigation is ongoing - this is the largest identification of suspected unlawful vapes we've seen to date," federal health minister Mark Butler said.
"(We are) sending a clear message to those seeking to supply vapes."
The haul is on top of the more than one million illegal vapes that have been seized by the goods authority and Australian Border Force since tough new import regulations came into effect at the start of the year.
Commonwealth, state and territory agencies are working together to control the product, which has hooked a new generation on nicotine.
Border force has also been working with officials in several countries to prevent the export of vapes to Australia, where it is permissible under the laws of that country.
"Now we need parliament to pass our legislation to return vaping to its original purpose of helping hardened smokers to quit - as prescribed by their doctor and purchased at a pharmacy like any other prescription," Mr Butler said.
The federal government's next round of vaping reforms will regulate vaping products as a therapeutic good, banning the import, manufacture, supply, commercial possession and advertisement of disposable single-use and non-therapeutic vapes.
Vapes containing nicotine can still be prescribed as an aid to quit smoking or to manage nicotine dependence.
Federal Labor MP Josh Burns, whose electorate of Macnamara takes in Port Melbourne, said parents and teachers in his seat were worried about the impact of vapes on school children.
"Vaping is a real concern in our community, and I'm pleased that Australian Border Force is taking action - including at the ports in Melbourne - to stop illegal vapes from hitting the streets," Mr Burns said.
"I'm proud to be part of a government that is taking the fight to Big Tobacco and to criminals who are breaking the law to make a buck off vulnerable young people."
