Wrightbus, the firm which built London's iconic red double-decker Routemaster, is set to collapse, leaving 1,200 employees without a job.
The Unite union warned of "devastating consequences" for the workforce, which manufactured the so-called 'Boris bus' ordered by Boris Johnson when he was London mayor.
The firm, which had been hugely profitable in the past based on its business model of producing low-emissions vehicles, went into administration on Wednesday.
It is one of Northern Ireland's largest employers and its loss is a major blow in the same week as travel firm Thomas Cook's collapse.
The Prime Minister has been urged to "do something decent" and intervene on behalf of one of the UK's main bus manufacturers.
Regional secretary Jackie Pollock said Wrightbus went in administration on Wednesday morning, adding: "This is a workforce at the cutting edge of technological advancements in the design and supply of green public transport.
"We cannot afford to lose any more jobs or skills in this area. Just three months ago Boris Johnson gave assurances that he 'will do everything we can to ensure the future of that great UK company'. He has a chance today to do something decent."
Mr Pollock said 1,400 workers and 1,700 supply chain jobs were threatened even though Ballymena-based Wrightbus had a "world-class" product.
Meanwhile administrators Michael Magnay and Peter Allen from Deloitte said the various Wrightbus companies had around 1,250 employees and the lack of a buyer "unfortunately means approximately 1,200 redundancies are being made today".
Mr Magnay said: "It is bitterly disappointing for all concerned that despite extensive efforts over recent months it has not been possible to find a buyer who wanted to maintain the business as a going concern.
"We recognise the companies are crucially important employers in Ballymena and this will be devastating news for those who worked there, their families and the town, which has already suffered from a number of manufacturing closures in recent years."
Worker Gordon Mairs expressed disgust after dedicating decades to his job, saying: "I feel angry, disappointed and let down."
"Officially we were made redundant this morning, we have no jobs. Twenty-two years I have been an employee." He started as an apprentice and worked his way up to become a quality inspector.
DUP MP Ian Paisley confirmed the administration process will begin on Wednesday, telling the BBC: "Essentially from this point the administrator has a week to find a buyer."
The North Antrim firm has been seeking investment or a new owner as it struggles with cash problems.
Stormont Assembly member Jim Allister said: "The impending administration of Wrightbus is devastating news, not just for the employees of Wrightbus but the wider North Antrim community and supply chain.
"My heart goes out to the hundreds with no wage packet this week or job hereafter."
Northern Ireland's manufacturing industry has been under pressure in recent years with the slumping into administration of Harland and Wolff shipyard in Belfast.
Michelin Tyres and Gallaher's Tobacco firms have also closed in Ballymena.
The company built the new Routemasters after Mr Johnson announced a lucrative order to produce the capital's latest fleet of buses.
Critics at the time said the new "Boris buses" were too expensive and estimated that the first eight had cost £1.4 million each to design and build.
The deal was worth £62 million and took the number of Routemasters on the streets of London to 1,000.
Wrightbus founder William Wright has been a prominent supporter of Brexit and the DUP.
