George Osborne has warned blocking Brexit risks "putting Parliament against people" and provoking a "deep constitutional crisis" in Britain.
The former chancellor added people who already feel estranged would be alienated further as he pledged to back legislation designed to allow Prime Minister Theresa May to start the formal Brexit talks.
His remarks came after Labour former leader Ed Miliband warned Mrs May against feeling an inevitable consequence of leaving the EU is being "driven into the arms" of US president Donald Trump.
Mr Osborne reiterated he argued "passionately" during the referendum campaign that leaving the EU would weaken Britain's trade links and diminish the country on the world stage.
Speaking during the second day of debate on the European Union (Notification Of Withdrawal) Bill, the Tory MP said: "I made those arguments and it saddens me that Britain and Brexit is bracketed in the same group as other isolationist and nativist movements around the world at the moment, and that we should strive to be - as the Prime Minister says - a more global Britain.
"But I lost the case. I made it with passion, I sacrificed my position in government for it and in the end we have to now accept that in a democracy the majority has spoken.
"Whilst I am a passionate believer in an open, internationalist, free-trading Britain, I'm also a passionate believer in Britain as a democracy."
Mr Osborne said it is "unfashionable in schools these days" to teach what he believes is a "true tale" of Britain's history, including Magna Carta, the Glorious Revolution, the Founding Fathers of the American constitution, the Great Reform Act and female emancipation.
He went on: "We have given the modern world a version of democracy that has spread far beyond our shores.
"And therefore to vote against the majority verdict of the largest democratic exercise in British history I think would risk putting Parliament against people, I think it would provoke a deep constitutional crisis in our country, I think it would alienate people who already feel they are alienated, and I am not prepared to do that."
"So I will be voting for the Bill tonight."
Mr Osborne said the Government had chosen "not to make the economy the priority in this negotiation, they have prioritised immigration control".
He also claimed the EU's priority will be to "maintain the integrity of the remaining 27 members of the European Union", adding: "They are not interested in a long and complex hybrid agreement with the United Kingdom and so therefore both sides at the moment are heading for a clean break from the European Union for the United Kingdom."
The former chancellor said it is "obvious" the Government will seek to secure a transitional agreement with the EU because "it's simply not possible for this Parliament to introduce all the domestic legislation that is going to be required" to replicate the current state of affairs.
He said negotiations will be a "trade off, as all divorces are, between access and money" as the UK seeks to reduce its financial commitments to the bloc.
Mr Osborne warned negotiations are likely to be "rather bitter" as he also committed himself to the battle ahead, predicting there will be "lively debate" in Parliament on issues such as immigration, state aid and agricultural policy.
"I will be in those fights in the couple of years ahead," he said.
Mrs May earlier used Prime Minister's Questions to urge MPs to vote for the Bill, saying: "This House has a very simple decision to make - we gave the right of judgment on this issue to the British people, they made their choice, they want to leave the EU.
"The question every member must ask themselves as they go through the lobbies tonight is, do they trust the people?"
MPs tabled a number of amendments designed to block the passage of the Bill, with Speaker John Bercow selecting one in the name of SNP Westminster leader Angus Robertson.
The amendment calls for the Bill not to be given a second reading for several reasons, including because the Government has yet to publish its detailed Brexit plans in a White Paper and because no details for "effective consultation" with devolved administrations on implementing Article 50 have been outlined.
Ministers were forced to bring forward the proposed legislation after the Supreme Court ruled that Parliament's approval is needed before the two-year Brexit withdrawal process can begin.
The Government wants this to start before the end of March.
Opening the second day of the debate, Mr Miliband said he accepted the referendum result - adding he will vote for the Bill to receive a second reading.
He said: "Part of the reason why I'll be voting the way I will tonight is I think this referendum in part stemmed from a deep frustration about politics and the sense of disaffection from politics that there is in the country.
"Therefore I think a heightened reason for saying that this process must begin is we do not want to give the sense that people, having voted for Brexit because they felt they'd been ignored, are being ignored once again."
Mr Miliband expressed concern about the lack of an objective economic analysis over the implications of Brexit and the time-scale being pursued by the Government for negotiations.
Labour's Rupa Huq (Ealing Central and Acton) said without the safeguards sought by Mr Miliband "there may be a crock of something at the end of the rainbow - but it just may not be gold".
Mr Miliband also expressed concerns over the Government's desire to work with Mr Trump, noting: "I can go along with the Prime Minister that Brexit means Brexit but I cannot go along with the idea that Brexit means Trump.
"And nor do I believe that is inevitable and nor do I believe that is what the British people want either.
"The danger is this, the Prime Minister feels it is an inevitable consequence of the decision to leave the EU that we are driven into the arms of president Trump."
The Labour MP called on ministers to outline a strategy which shows the country values its role in Europe, adding countries on the continent fear the UK is "throwing in our lot with President Trump and turning our back on them".
He said: "No good will come of this. These are the tests of who we are as a nation, our values and how we intend to apply them in the years ahead."
Conservative former minister Alistair Burt, who backed Remain and said he will support the Bill at second reading, said: "I'm not giving up fighting.
"I want to see the very best for my constituents out of the new arrangements."
He added: "I don't believe that this Bill provides much opportunity for the addition of detail to Government future negotiation - the Government needs a pretty open hand - though one or two amendments might help the Government in keeping and retaining parliamentary support.
"I will fight for a negotiated settlement, watching carefully for any sign that no deal is moving up the agenda.
"I want the Government to be as open as possible to as many options as possible."
Mr Burt, after recognising there are divisions in the country, also said he does not want the next generation of Tory MPs to have "the blight of this argument dogging them, their associations and their members and voters the same way it has dogged us".
He went on: "It soured friendships, deepened bitternesses and damaged relationships - and I swore at a mate in the tearoom, and I'm sorry."