Cabinet Office minister David Lidington, who chairs several Brexit ministerial committees, said the suggestion by some EU leaders that Britain might change its mind about leaving the bloc was a "red herring".
"Having taken a decision by a referendum, I don't see that changing," he told the Daily Telegraph newspaper in an interview.
However, he added: "We may be looking in a generation's time at an EU that is configured differently from what it is today.
Lidington was appointed earlier this month to his post, which involves standing in for Prime Minister Theresa May in parliament and deputy chairing cabinet meetings.
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He opposed Brexit in the 2016 EU referendum, but said most Britons did not want to be part of the EU as it stands -- and were unlikely to change their minds as the bloc moves towards greater economic and political integration.
He noted that Britain will remain part of the NATO military alliance, the Organization for Security and Co- operation in Europe, and the Council of Europe human rights watchdog.
"I can't predict sitting here today what that network of organisations and alliances including the EU, how that will change or is going to look in 10 years or 20 years time," he said.
EU President Donald Tusk said this week that the bloc's "hearts are open" to Britain changing its mind.
Britain began the two-year Brexit process last year, putting it on course to end its four-decade membership of the EU on March 29, 2019.