Sir Leon, vice-president of the European Commission, said the party should not be lulled into believing that its success in the European elections would be matched in a Westminster poll.
In his most critical comments to date on Mr Hague's strategy, the former Tory cabinet minister said a similar "negative" campaign for the general election would be highly divisive within the party.
Sir Leon also criticised Tony Blair for failing to use the European elections to put a strong case in favour of the UK joining the single currency.
However, Mr Hague's tactics caused the former home secretary the most concern and he warned that while the anti-euro campaign would attract some Conservatives it would "turn off" the rest of the voters."It risks being, although a short-term benefit, a historically, strategically wrong miscalculation. It can lull you into a false sense of security and actually lead people into thinking that if you follow this anti-European route it's going to win," he told the BBC's On the Record programme.
"A 24 per cent turn-out is of no significance and it could, in fact, lure you into electoral disaster again. It certainly won't indicate anything as far as the result of the general election."
Sir Leon added that many Tories, including Kenneth Clarke and Michael Heseltine, had kept silent during the European campaign but felt "uncomfortable" with its message.
The strident anti-European tone of Mr Hague's campaign appeared to rule out joining the euro for ever and risked ending the fragile truce that had been crafted between the two wings of the party, he suggested.
"The kind of emotional hostility to the single currency ... makes it difficult to take the concept of open-mindedness, which the idea of waiting a period of time implies, as being seriously what is meant now."
The Prime Minister had also let down the country by refusing to confront openly the question of Britain's membership of the single currency, he said.
"He has got to show the leadership and come out and say, `Yes, I think it's a good idea' and then persuade people," Sir Leon said. "You can't expect the business community and the opposition parties to do your work for you if you're not prepared to take a lead yourself."