David Macdonald, an independent councillor on East Renfrewshire Council, said he would now vote for the Lib Dems on May 23.
But his name will still appear on ballot papers as a Change UK candidate as it is too late for it to be removed.
It is the second time Change UK has lost its lead candidate north of the Border. Last month, Joseph Russo stood down after claiming he he was “not fully prepared” for the “personal scrutiny” he faced after “offensive” online posts came to light.
Speaking outside Holyrood alongside Scottish Liberal Democrat leader Willie Rennie, Mr Macdonald said the numbers “don’t look good” for Change UK in Scotland, and that voters should instead back the “fundamentally similar” pro-EU and pro-UK platform of the Lib Dems.
“They share many of the values of Change UK and are now the most likely party in favour of both remaining in the EU and of Scotland remaining in the UK to have a chance of being elected.”
The resignation of Cllr Macdonald will raise further questions about how Change UK vetted its prospective candidates.
Paul Masterton, the Conservative MP for East Renfrewshire, said: “I assume Mr MacDonald, who was elected as an independent onto East Renfrewshire Council in 2017, and has spent two years demanding party politics be removed from local government, will now be stepping down and fighting a by-election in his new colours?”
Change UK was registered as a political party to allow the breakaway group of Conservative and Labour MPs, formerly known as the Independent Group, to contest the European elections.
Chuka Umunna, a former Labour MP and an original member of the breakaway group, said it was “disappointing” that Macdonald had quit.
He added: “It is obviously disappointing that this candidate has chosen to pledge allegiance to another party - he has let down his fellow candidates and activists.
“But we are focusing all our efforts on adding to the Remain vote in the UK and challenging the pro-Brexit Tory, Brexit and Labour parties, which is why our leader challenged Nigel Farage to a live TV debate this week.
“In the past 24 hour’s Labour’s former head of campaigns for the the North of England has come out for Change UK, as have many former Labour voters. Winning voters over from the main parties and growing the Remain vote across the UK will continue to be our focus.”