Airbus has warned that it could move wing-building out of the UK in the future if there is a no-deal Brexit.
The planemaker's chief executive, Tom Enders, said Airbus "will have to make potentially very harmful decisions for the UK" in the event of no deal.
He said it was a "disgrace" that firms could still not plan for Brexit.
His remarks were welcomed by Business Minister Richard Harrington, who said Airbus was correct to warn of the dangers of a no-deal scenario.
"Crashing out is a disaster for business," Mr Harrington told a meeting at the German embassy on Thursday morning.
"Airbus is correct to say it publicly about and I'm delighted they have done so," he added.
In all, Airbus employs 14,000 people in the UK.
That includes 6,000 jobs at its main wings factory at Broughton in Wales, as well as 3,000 at Filton, near Bristol, where wings are designed and supported.
Mr Enders said: "Please don't listen to the Brexiteers' madness which asserts that, because we have huge plants here, we will not move and we will always be here. They are wrong."
Responding to Airbus's statement, a government spokesperson said: "The UK is a world leader in aerospace. We are the home of the jet engine, the wing factory of the world and are world-renowned for our skills and capabilities in the most technically-advanced parts of aerospace manufacturing.
"It remains our top priority to leave the EU with a good deal; a deal that is good for business, will protect jobs and prosperity, and provide the certainty that business needs."
Airbus's latest intervention follows announcements by two other companies that they were moving their headquarters out of the UK.
Sony said it would transfer its European HQ from the UK to the Netherlands to avoid disruptions caused by Brexit.
And appliance maker Dyson announced it was moving its headquarters to Singapore, from Malmesbury in Wiltshire, although it said the decision had nothing to do with Brexit.
However, another firm, Japanese technology company Fujitsu, told the BBC it had "zero intention" of moving its operations out of London.
Duncan Tait, Fujitsu's European boss, said it had "a thriving business in the UK", adding: "We're recruiting people every week."
Mr Enders said that while the world's second-largest aerospace group could not "pick up and move our large UK factories to other parts of the world immediately", Airbus could be "forced to redirect future investments in the event of a no-deal Brexit".
"And make no mistake, there are plenty of countries out there who would love to build the wings for Airbus aircraft," he added.
"Brexit is threatening to destroy a century of development based on education, research and human capital."
Katherine Bennett, senior vice-president of Airbus in the UK, reinforced Mr Enders' message.
She told the BBC that a no-deal Brexit would be "catastrophic" for her business, with "chaos at the borders" that would hold up delivery of vital components.
This is not the first time that Airbus has warned of the consequences for its business of a no-deal Brexit.
Last year, it issued a risk assessment saying that if the UK left the EU without a withdrawal deal, it "would force Airbus to reconsider its investments in the UK and its long-term footprint in the country".
However, Mr Enders' latest remarks suggest that the firm has toughened its stance since then.
MPs are putting forward alternative plans to Theresa May's Brexit plan after it was voted down by Parliament last week.
The UK is due to leave the EU on 29 March this year.
by Theo Leggett, BBC business correspondent
The gloves are off. That's the clear message from Airbus' pugnacious chief executive, Tom Enders.
Opposition to Brexit from Airbus is not new. The company warned of the potential dangers to its business even before the referendum had taken place.
Since then, the rhetoric has been steadily ramped up. Last year, the company published a "Brexit Risk Assessment", in which it warned that leaving without a deal would be "catastrophic" for its business.
We've had warnings about the risk to future investment before, but now the threat is much more explicit and the language is much more forthright. The failure to come up with a clear plan is a "disgrace". Other countries would "love" to build the aircraft wings currently made at Broughton.
There's even a warning not to listen to "the Brexiteers' madness". The time for diplomacy, it seems, is past.
So what's changed? The company clearly believes that the risk of "no deal" is growing, thanks to the impasse in the House of Commons.
And as a business which relies on the rapid transfer of parts from the UK to assembly lines in France and Germany, it is very exposed to any delays in shipments - or problems getting new safety certification.
Meanwhile, Tom Enders is due to leave his job in April. So perhaps he's in a very good position to talk tough, without worrying whom he's upsetting in the process.