The cross-party politicians said they feared leaving the EU without securing a deal would lead to job losses and badly affect the UK's manufacturing industry.
Dame Caroline Spelman, the Conservative politician and Christian, orchestrated the letter.
She told Premier life would get worse for many if the UK leaves the EU without an agreement on 29th March.
"This may not be a perfect deal but I think this is one where we need to actually really think about the true human cost of what we're about to do and listen very carefully to what our heavenly father has to say," she said.
"I've got unemployed workers coming into my constituency surgeries who've lost their jobs, who can't pay their mortgages. This is not scare-mongering, this is the reality and it will get worse if we leave without a deal."
All 209 signatories to the letter have been invited to meet the Prime Minister in Downing Street on Tuesday.
The letter comes as Mrs May is set to increase her efforts to persuade her Brexit critics and get guarantees from Brussels ahead of the vote on the blueprint of the deal on 15th January.
Dame Caroline highlighted the importance of MPs like Labour's Jack Dromey (pictured above) signing the letter: "People keep saying to me, 'come on you MPs, we want you to work together cross party'.
"Look, here it is - this is a grass-roots, back-bench movement involving MPs from all parties, all parts of the UK, appealing to the prime minister.
"It's a critical moment - I think probably the most serious moment in our politics in the last 40 years.
"Here is where we need to get down on our knees and pray that the prime minister will have the wisdom and the MPs will have the courage to do the right thing."
Meanwhile, an exercise involving nearly 100 lorries was carried out in Kent to test how Britain's roads will cope if there is a 'no-deal' Brexit.
Listen to Premier's Alex Williams speaking with Dame Caroline Spelman:
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