Boris Johnson described Conservatives wanting to break away from the party to join Ukip as "utterly nuts", and warned such actions would "let this country sleepwalk into a Labour government".
His outburst comes as two Conservative MPs Douglas Carswell and Mark Reckless defected to Ukip. Reckless, MP for Rochester and Strood, announced his decision to defect on the eve of the Tory party conference, now prompting a by-election.
Clacton MP Carswell announced his defection to the Eurosceptic party in August.
Writing in his column in the Daily Telegraph, Johnson blasted the "would-be jumpers" and the "auto-defenstrators" in the party, who want to "launch themselves headlong into the silage" as "utterly nuts".
"If you really want to let this country sleepwalk into a Labour government, then that is your prerogative. You can close your eyes and let it happen. You kip if you want to; the rest of us are going to fight and win," he wrote.
Reckless said he had not taken the decision lightly but blamed the Tory leadership as "part of the problem that is holding our country back".
He said the electorate had little confidence in "an immigration system where we turn away the best and brightest from our Commonwealth in order to "make room for unskilled immigration from southern and eastern Europe".
"I promise to cut immigration while treating people fairly and humanely.
"I cannot keep that promise as a Conservative. I can keep it as Ukip," he added.
But in defiant support of the Prime Minister, Boris, who has been nominated as Tory candidate for Uxbridge and South Ruislip at the next election, said Cameron was the only man who could give people their say over the future of the UK relationship's with Europe.
He said: "My dear fellow Eurosceptic: there is only one prime minister in the current EU who is capable of collating that support and turning it into a new treaty, and only one man who is going to be able to give the people of this country the vote on the EU that we have been deprived of for the past 40 years, and that man is David Cameron.
"There are only two people who are in a position to take the keys to Downing Street next May, and "they are David Cameron or Ed Miliband. I know that you disagree vehemently with most of what Ed Miliband says and does – and so I must urge you not to allow the disaster of a Miliband premiership".
The Tory party suffered further embarrassment over the weekend after cabinet minister Brooks Newmark resigned after being exposed by the Sunday Mirror for sending explicit photos of himself on Twitter to a Tory PR girl, named Sophie Wittams - including shots of himself in paisley pyjamas. Wittams turned out to a male journalist investigating the "inappropriate use of social media by MPs".