Michael Moore has been sacked as secretary of state for Scotland and replaced by Alistair Carmichael, another senior Liberal Democrat.
The move comes as a reshuffle of Conservative and Lib Dem ministers in the coalition government is under way.
Mr Moore was a leading figure in the No campaign ahead of the referendum on Scottish independence next September.
Labour leader Ed Miliband is also planning a shake-up of his frontbench team on Monday.
The BBC understands Mr Moore is the only cabinet minister on the Lib Dem side of the coalition to lose his job in the reshuffle, which is expected to focus on middle-ranking ministerial positions.
BBC political correspondent Tim Reid said Mr Moore was "disappointed".
'Formidable'Mr Carmichael, the MP for Orkney and Shetland, has been the Lib Dems' chief whip since the formation of the coalition government. He was previously the party's Scottish spokesman.
The BBC's chief political correspondent, Norman Smith, said the move could be explained by Prime Minister David Cameron and Deputy Prime Minister Nick Clegg's desire to have a more combative figure in the job to take the fight to SNP leader Alex Salmond.
In his resignation letter, Mr Moore said it was a "hugely important time" in Scottish politics and that he was "grateful" for having been able to make the case for Scotland to remain part of the UK.
In his response, Mr Clegg said Mr Moore had done a "formidable" job but that he believed "we now need to draw on different experience in the final year running up to the referendum itself".
In a tweet, Mr Cameron confirmed that a reshuffle was under way, with news on individual appointments likely to be broken via social media.
A number of Conservative ministers have resigned from the government in recent days in anticipation of the reshuffle, with Mr Cameron looking to reshape his lower and middle ranks.
Simon Burns, John Randall and Chloe Smith have all announced they are standing down.
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