Sixty MPs representing constituencies with manufacturing industries have urged Theresa May to rule out a no-deal Brexit.
Birmingham MP Jack Dromey (Lab Erdington) and Solihull MP Caroline Spelman (Con Meriden) have organised the letter, which is signed by MPs from across the country.
The letter said: "Manufacturing plants employ thousands of our constituents and their jobs will be put at immediate risk if the United Kingdom leaves the European Union with no deal."
And referring to the day the UK is set to leave the EU, they said: "We are acutely aware that 29th March is fast approaching."
Nobody knows whether the Prime Minister will succeed in getting EU leaders to agree a Brexit withdrawal agreement that Parliament is willing to accept, or what will happen if she doesn't.
But the MPs said it was essential that she rules out the option of leaving the EU with no deal at all, in order to save manufacturing jobs.
Mr Dromey and Mrs Spelman both represent constituencies that are home to thousands of Jaguar Land Rover staff, at the firm's Solihull plant and the Castle Bromwich plant in Erdington.
It has been reported that JLR intends to axe thousands of roles, partly due to slow sales in China and lack of demand for diesel cars but also because of continued uncertainty about Brexit.
Major manufacturers have warned that they depend on the easy import of parts from across the EU in order to keep factories operating efficiently.
This would become impossible if the UK quits the EU without a deal allowing goods to pass through borders without checks.
But if big manufacturers reduce or end investment in the UK then the consequences would also be devastating for British suppliers of parts.
UK firms have also enjoyed success selling products in EU markets.
The letter states: "The renaissance of manufacturing and its supply chains in this country, bolstered by demand for exports, has markedly improved the lives of our constituents.
"The principal market for these exports has been the European Union."
Big manufacturers would move jobs to EU countries if the UK quits without a trade deal, the MPs warned.
They said: "Leaving without a deal would make continued investment in UK manufacturing a real challenge for global firms, when they have plants in other European locations
"Without continued investment and confidence in the UK manufacturing sector, thousands of jobs across the country will be put at immediate risk."
Former Conservative Cabinet Minister Nicky Morgan is among MPs signing the letter. Others include former Attorney General Dominic Grieve and Conservative backbencher Anna Soubry.
Mrs May has been attempting to persuade EU leaders to add reassurances to her proposed withdrawal agreement about the "backstop", a plan to prevent a hard border between Ireland and Northern Ireland, in order to make it more acceptable to MPs.
But she also said in a House of Commons statement last week that the Government was stepping up preparations for a "no-deal" Brexit, in case her attempts fail.
The Prime Minister is to condemn calls for a second Brexit referendum, as Cabinet tensions on EU withdrawal continue to break into the open.
She is to use an address to the Commons to say a new national poll would do "irreparable damage" to the integrity of British politics.
The PM will say: "Let us not break faith with the British people by trying to stage another referendum."
MPs who have signed the letter include:
Matt Western, Labour MP for Warwick and Leamington
Mark Pawsey, Conservative MP for Rugby
Jeremy Lefroy, Conservative MP for Stafford
Marcus Jones, Conservative MP for Nuneaton
Mark Garnier, Conservative MP for Wyre Forest
Preet Gill, Labour MP for Birmingham Edgbaston
Jim Cunningham, LAbour MP for Coventry South
Khalid Mahmood, Labour MP for Birmingham Perry Barr
Ian Austin, Labour MP for Dudley North
Richard Burden, LAbour MP for Birmingham Northfield
Steve McCabe, Labour MP for Birmingham Selly Oak
Emma Reynolds, Labour MP for Wolverhampton North East
Colleen Fletcher, Labour MP for Coventry North East
Liam Byrne, Labour MP for Birmingham Hodge Hill
Roger Godsiff, Labour MP for Birmingham Hall Green
Shabana Mahmood, Labour MP for Birmingham Ladywood
Pat McFadden, Labour MP for Wolverhampton