According to police, the small tobacco seedlings had an estimated worth of about $20 million at maturity.
They were allegedly located and destroyed by police with the authorisation of the Australian Taxation Office.
The seizure came after eight warrants were executed at residential and rural addresses in Shepparton and Mooroopna.
Tobacco machinery, a quantity of illicit tobacco, cash, stolen vehicle registration plates and ammunition were also allegedly seized during the searches.
Police from the Echo Taskforce, Eastern Region Crime Team and Shepparton local area were joined by Australian Border Force and the Australian Federal Police for the searches.
A 36-year-old man, a 38-year-old man, a 34-year-old man and a 41-year-old man, all from Shepparton, were arrested and are expected to be charged on summons with a range of offences including possessing the proceeds of crime and firearms offences, as well as a range of Commonwealth offences, police said.
The men have been released pending further inquiries.
The investigation remains ongoing.
Police said the purchase of illicit tobacco in Australia put more than $600 million each year into the hands of criminals and undermined the efforts of businesses trying to turn a legitimate profit.
This activity was a significant blow to the illicit tobacco trade in Australia, police said.
Anyone with further information is urged to contact Crime Stoppers on 1800 333 000 or submit a confidential crime report to www.crimestoppersvic.com.au