Conservative MP George Eustice has resigned as agriculture minister, citing fears that Brexit could be delayed.
In his resignation letter to the prime minister, the MP for Camborne and Redruth said he wants to be "free to participate in the critical debate that will take place" in the coming weeks.
Mr Eustice said he fears events in Parliament this week "will lead to a series of events culminating in the EU dictating the terms of any extension requested and the final humiliation of our country".
He said he would vote for Mrs May's deal when it comes back before MPs, but added that Britain should not be fearful of leaving without a deal.
It is with tremendous sadness that I have decided to resign from the government following the decision this week to allow the postponement of our exit from the EU. Since Parliament is now in direct control of events, I want to be free to participate in the critical debate that will take place in the weeks ahead. I will vote for your Withdrawal Agreement when it returns to the House and I very much hope that the Attorney General succeeds in securing final changes so that others might too.
Analysis by ITV News West Country political correspondent David Wood:
George Eustice was one of the leading Brexit campaigners in the West Country.
From a farming family he was clear the advantages that leaving the EU could have on the farming and fishing industry.
As a minister, Eustice has only been able to publicly comment on Brexit through the subjects of his, now former ministerial brief, of fishing and farming.
Key Brexit pieces of legislation have been going through the house in recent weeks and I understand he was keen to see those through. He has also recently spoken out about how damaging a 'no deal' Brexit could be for the country.
That said, his letter today resigning from the Government shows his frustration about the progress of our EU exit.
Theresa May has made it clear she will give MPs a vote on extending our exit time IF her Brexit deal isn't voted through in the next couple of weeks.
I fear that developments this week will lead to a sequence of events culminating in the EU dictating the terms of any extension requested and the final humiliation of our country.
He goes on to say that he will continue to support the PM's Brexit deal and hopes that changes can be made to it that would encourage other MPs to back it.
He warns that also not having the threat of a 'no deal' Brexit undermines the UK's negotiating position: "We must therefore have the courage, if necessary, to reclaim our freedom first and talk afterwards."
Ultimately, the Cornish MP's decision is a blow to Theresa May. He has been leading on key pieces of Brexit legislation, has been a loyal minister and a long serving minister - I can count on one hand how many ministers have stayed in the same job as long as he has.
Click here to read Robert Peston's thoughts on Mr Eustice's resignation.