The Daily Mail has broke with its sister paper The Mail on Sunday to formally back the campaign for Britain to leave the EU.
In a two-page editorial, the newspaper argued it was best for the country to vote to leave the union in Thursday's referendum.
The declaration came two days after its sister publication The Mail on Sunday - which is a separate publication with a different editorial team - urged its readers to vote Remain.
It warned that "by any calculation" Britain would face higher tariff and economic uncertainty, saying it was "not the time to risk the peace and prosperity" of the UK.
The split has been interpreted by some media watchers as indicative of a split within both papers' parent company, Associated Newspapers, over the issue.
Journalists said it was an example of the editors choosing the stance of their own papers without the influence of their proprietor, Lord Northcliffe.
The Mail on Sunday has been edited by Geordie Gregg since 2012 and Paul Dacre has edited The Daily Mail for more than 20 years.
Despite this, the national paper's declaration has not been included on the front page of its Scottish edition.
The Scottish Daily Mail has run on a different front page story about David Cameron's plea for voters not to "let Brexit destroy the union".
Scottish voters are widely regarded as fair more pro-EU than their English neighbours and there have been warnings that the country will face calls for a second independence referendum if Britain as a whole votes to quit.
The papers are not the first to come to different conclusions about their stance.
Last week The Times declared for Remain whereas its sister title, The Sunday Times, opted for Leave.
Its stablemate, The Sun, also choose Leave which some on Twitter have said was due to the influence of its proprietor, Rupert Murdoch, - a charge denied by its associate editor Trevor Kavanagh.
The Daily Mail's decision will come as no surprise to some as many commentators noted the paper's largely anti-immigration stance over the past few years.
A study by Loughborough University analysing media coverage of the referendum found that The Daily Mail was the second most pro-Brexit daily newspapers after The Daily Express - which has campaigned for the country to leave the EU for several years.
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