Theresa May's Brexit deal is "doomed" and must be renegotiated, ex-defence secretary Sir Michael Fallon has said.
Sir Michael launched a scathing attack on the proposed EU agreement, saying it was the "worst of all worlds".
Asked whether Mrs May should stay on as Tory leader if it was rejected by MPs, he said it was "up to my colleagues".
The BBC's Laura Kuenssberg said he was "not one of the usual suspects" on Europe and his remarks showed the depth of Conservative opposition to the deal.
Parliament will vote on whether to accept or reject the terms of the UK's withdrawal and future relations negotiated by Mrs May on 11 Decembe
Sir Michael's decision to come out against the deal is a blow to the prime minister, who is struggling to muster support in Parliament for it.
Labour, the Lib Dems, the SNP and the Democratic Unionists have said they will vote against the deal while many Tories have said publicly they are opposed.
Opponents of the deal say it will keep the UK too closely tied to EU rules and make it harder to strike future trade deals with other countries and minimise their value.
US President Donald Trump told reporters on Sunday the withdrawal agreement "sounds like a great deal for the EU" and meant the UK might not be able to trade with the US.
In other developments:
- Other political parties have demanded to be involved in any televised Brexit debate, after Theresa May challenged Jeremy Corbyn to a head-to-head encounter
- Research published by the London School of Economics, King's College and the Institute for Fiscal Studies suggests the PM's Brexit deal could leave the economy as much as 5.5% smaller in 10 years time than it would be if the UK stayed in the EU
- Judges at the European Court of Justice examining whether the UK can call off the process of leaving the EU without permission from member states, following a challenge by a group of Scottish politicians
- International Trade Secretary Liam Fox is visiting Israel to boost economic ties ahead of Brexit
Fallon on PM's 'huge gamble'
Sir Michael Fallon, who served as defence secretary under David Cameron and Theresa May
before having to resign a year ago, told MPs on Monday the agreement was a "huge gamble" as it would see the UK give up its power to influence EU rules and regulations in return for vague assurances over future trade arrangements.
He told BBC Radio 4's Today that "this is not a good deal and we need a better deal", saying that Mr Trump's criticism of its repercussions for transatlantic relations "could not simply be brushed off".
"My fear is that this deal gives us the worst of all worlds," he said. "No guarantee of smooth trade in the future and no ability to reduce the tariffs that we need to conclude trade deals with the rest of the world.
"So, unless the House of Commons can be persuaded somehow that those are possible then I think, yes, the deal is doomed."
Asked if Mrs May was also doomed, he replied "that's up to my colleagues", while stressing that a change of leader would not necessarily address the difficulties the UK now found itself in.
When it was put to him that did not sound like an endorsement of Mrs May, he replied "take it any way you want".
Could Brexit be delayed?
Sir Michael said the 29 March 2019 date for Brexit, which is enshrined in UK law, may have to be pushed back to give negotiators the time to make major improvements to the agreement.
All 28 EU states would need to agree to extend the Article 50 process of negotiations to allow this to happen, something Theresa May has repeatedly ruled out.
Cabinet Office David Lidington said he did not think doing this "would get us anywhere" as the EU had made clear this was the only deal on the table.
He told Today there was no "Plan B" and the agreement was a "decent compromise" which would provide a springboard to the next stage of negotiations on the two sides' future relationship.
The prime minister is continuing to making the case for the agreement, which she says delivers on the 2016 referendum vote in key areas and is in the national interest.
During visits to Wales and Northern Ireland, she will meet business and political leaders and argue that it gives certainty to farmers and other businesses.
Under the proposed agreement, the UK would not be able to complete any trade deal with a country outside the EU until the end of the proposed transition period - currently scheduled to last until 31 December 2020.
In reality, any bilateral agreement between the UK and the US is likely to take years to negotiate given its complexity, differing standards in areas such as agriculture, and the fact it would require ratification by the US Congress.