The drugs den, containing more than 350 plants, was found in the basement of a property in Victoria Street on Monday.
West Midlands Police arrested two men, aged 41 and 46, on suspicion of growing cannabis.
A total of 363 plants were seized, along with equipment for growing cannabis.
The items will be forensically examined before being destroyed.
A spokesman for West Midlands Police said: "We've seized more than 350 plants and arrested two men after officers carried out a drugs warrant in Wolverhampton city centre.
"Officers found 363 plants in the basement of a property in Victoria Street at just after 9am on Monday morning.
"Equipment for growing cannabis on a large scale was also seized, and along with the plants, will be forensically examined, before being destroyed.
"Two men, aged 41 and 46, were arrested on suspicion of producing cannabis. Following questioning, they have been released pending further investigations.
"Every cannabis farm we destroy helps prevent a vicious circle.
"The plants won’t end up as street deals, the profits won’t go on to fund other crime, and they won’t ruin lives or pollute our communities.
"If you think a property is being used as a drugs farm, there's a list of tell-tale signs, and advice on what you can do at west-midlands.police.uk/your-options/cannabis-factories."