Anna Soubry, Nicky Morgan and Ken Clarke backed an amendment giving MPs a legal guarantee of a vote on the final Brexit deal struck with Brussels.
It was the first Commons defeat for Theresa May as prime minister - losing by 309 votes to 305.
EU bill debate: Notts remainers cosy up
BBC East Midlands political editor
In the House of Commons, Ken Clarke has said we are slowly getting to the fundamental minimum a parliamentary democracy should be demanding: Full parliamentary approval.
Anna Soubry has moved seats to be next to him with asides of support.
Clarke: Government should welcome 'divorce settlement'
BBC Local Live
At Prime Minister's Questions today, Rushcliffe's Ken Clarke was the first to raise the Brexit Bill.
He said the economic benefits of the EU have always been so great as to justify payments made by members.
He asked Damian Green to welcome "a possible imminent settlement" on the so-called divorce bill, which would allow the government to "get on with serious negotiations to maximise future access to free trade".
Mr Green replied it would be "wrong to go into figures", but agreed ministers were focusing on "getting the possible deal so we can move on to trade talks".
And you're right, it is, but last year Chancellor Philip Hammond announced he would deliver the Budget in the Autumn, giving MPs longer to scrutinise it before the new tax year starts in April.
The last chancellor to give an Autumn Budget was Rushcliffe MP Ken Clarke in 1996.
The Budget is the only time alcohol is allowed in the chamber of the House of Commons.
Mr Clarke was also the last chancellor to bring in a Budget tipple in the 1990s - he liked a glass of Glenfarclas Scotch whisky to accompany his speeches.
Ken Clarke's Brexit speech met with applause
BBC Local Live
Rushcliffe MP Ken Clarke just received a round of sustained applause in the House of Commons after his EU bill debate speech.
The clapping - which isn't allowed under parliamentary convention - came after his killer closing line: "I am the rebel".
He said there were only two MPs still in the House, who were present in 1972 when the European Communities Act was passed: Labour MP for Bolsover Dennis Skinner and himself.
Pro-EU Mr Clarke adds that he and Mr Skinner have always voted in opposite ways on Europe and the government have more chance of support from Mr Skinner than from him.
He said the idea has been "put forward by UKIP and others that [the act] led faceless, grey Eurocrats to produce vast quantities of awful legislation and red tape is one of the biggest myths of our time".
But he paid tribute to former UKIP leader Nigel Farage's "campaigning abilities", calling him "the most successful politician of my generation".
He joked that people persuaded by Mr Farage "are all looking forward to bent bananas again once we actually repeal this piece of legislation".
Ken Clarke quips he's 'talking cricket' on EU visit
Some of the southern parts of the current Rushcliffe constituency would combine with Loughborough, to create a new Loughborough and South Rushcliffe seat.
Further south, some of the current South Leicestershire seat would become part of a new Daventry and Lutterworth constituency.
In Derbyshire and Derby, a new North East Derbyshire constituency will be created that is in line with its local authority of the
same name, and there will be a Bolsover constituency containing the entirety of Bolsover District.
There are no proposed changes to the Bassetlaw, High Peak, Leicester East, Leicester South, North West Leicestershire and Mansfield seats - but all the rest face some minor tweaks which you can see here.
Broxtowe's Anna Soubry has called for Prime Minister Theresa May to sack him over the latest in a string of controversial incidents, while Ruschliffe representative and Father of the House Ken Clarke also said the remarks were beyond the pale.
I think Boris has done himself enormous harm - he should go away and try and find something out about foreign policy and try to be foreign secretary.