The Melbourne venue, named after wartime Labor prime minister John Curtin, is more than 150 years old and one of Australia's oldest pubs.
Opposite the Victorian Trades Hall Council, the pub was a popular watering hole for Labor and union luminaries in its heyday, including former prime minister and Australian Council of Trade Unions boss Bob Hawke.
The pub's managers say its new owners have decided to sell after the previous landlord died, casting a cloud over the venue's future when the lease expires in November.
Operator Ben Russell said he had spoken to the building's brokers and it was likely to be bought by a developer and turned into apartments.
"It's a quarter block in Carlton. You don't have to be a genius to work out what the pub is going to be," he told reporters on Wednesday.
The publican said only the building's facade is safeguarded from development and urged Heritage Victoria to extend protection to the whole building.
"These culturally significant venues can't be getting knocked down all the time," he said.
Trades Hall Secretary Luke Hilakari said the union will lobby the government to extend heritage protection for the Curtin and other historic pubs, and even attempt to buy the venue.
He estimates it would cost about $6 million, with the Trades Hall needing other unions to chip in to mount a proper bid and secure its future.
Asked what Mr Hawke would say of the pub's potential demise, Mr Hilakari said: "You would be a mug to sell this pub to a developer ... and he'd finish it with a skull."
If those efforts fail, Mr Hilakari floated the prospect of a return to 1970s in the form of a union "green ban" to stop development.
"I would put a warning out there to developers who are thinking of trying to knock down the John Curtin: the union movement won't have it. We just simply won't have it," he said.
The union is keen to avoid a repeat of the illegal demolition of Carlton's Corkman Hotel in 2016, which resulted in its developers being fined more than $1 million and jailed after failing to turn the site into a public park.
Premier Daniel Andrews said that while the Curtin's future was a private commercial matter, Victorians would like to see the pub saved given its history.
"I'm sure the union movement and people who have enjoyed that first class establishment will get around it, and maybe (the owners) can revisit the decision they have made," he said.
Opposition Leader Matthew Guy said he would support a heritage listing of the pub.
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