"That won't work," the veteran minister told Germany's Der Spiegel weekly, which tomorrow plans to publish a German-English edition at home and in Britain with "Please don't go!" on the cover.'
"That would require the country to follow the rules of a club which right now it wants to leave."
If a majority of Britons opt for a Brexit in the June 23 referendum, it will shut the nation out of the single market with its free movement of people, goods and services, Schaeuble said.
The polls are on a knife's edge ahead of the referendum on whether Britain should stay in or leave the 28-country bloc.
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Schaeuble warned that a Brexit could spark contagion in the EU, according to excerpts of the interview due to appear in Der Spiegel's Saturday edition.
"How, for example, would the Netherlands react, given its traditionally very close ties to Britain?" he said.
Whatever the outcome, he added, the EU must show it has learned lessons from the British referendum.
"In response to a Brexit, we couldn't simply demand further integration," he said.
Even if a Brexit is narrowly averted, he said, "we would have to see it as a warning and a wake-up call not to continue with business as usual."
Schaeuble warned that a Brexit would hurt all sides, saying that "it would be a miracle if a British withdrawal would not have economic disadvantages".
On the continent, he said, eurozone finance ministers "are preparing for all possible scenarios in order to limit the dangers".
But if Britain leaves, Schaeuble added, Europe in the end "will manage without Britain".