The First Minister said that Mr Cameron’s “jaiket will be on a shoogly peg” if the Yes vote scores a victory in the referendum.
Mr Salmond was speaking at a rally in Edinburgh on the same day that Mr Cameron, along with Westminster party leader colleagues Nick Clegg and Ed Miliband, travelled to Scotland to campaign to keep Scotland in the United Kingdom.
Mr Salmond said he believed Mr Cameron would be in an “untenable position” if Scotland becomes independent.
“I think given the circumstances of how he has mishandled his leadership of the No campaign – it’s one thing to be upfront and come and debate in a proper way, but to send Alistair Darling as his front man and then stay in London until the last minute, then jetting up here to scaremonger – that’s a sign of a politician who does not appear to be leading from the front,” he said.
“All political parties, even the Tories, respond to leadership.
“If the people of Scotland choose to vote Yes next Thursday, and I’m not taking for granted that they will, then his jaiket will be on a shoogly peg.”
He added: “At least if he had fought the good fight fairly and squarely in this debate, then at least he could have said, ‘I’ve done everything I can’.”
Mr Cameron has previously insisted that he will not quit if Scotland leaves the UK, despite one unnamed senior minister claiming earlier this year that he would “go down in history as the prime minister who lost the Union”.
At the campaign event, which attracted around 200 pro-independence supporters to Edinburgh’s Piershill Square, Mr Salmond dismissed claims that the non-nationalist parties’ plan for extra powers for a Scottish Parliament could sway undecided voters to remain within the UK.
“Unfortunately, what they’re offering is too little, too late,” he said. “It’s too late because that’s what it is: a last-minute piece of desperation. It’s just a retread of what was offered in the spring.”
Mr Salmond also claimed that he believed US president Barack Obama’s support of the UK had been reluctant.
In June, Mr Obama said the US had “a deep interest” in making sure that Britain remains “strong, robust, united and an effective partner”.
But the US State Department earlier this week refused to repeat the president’s backing for the Union.
“I know David Cameron has been phoning up everyone and his auntie all over the world in order to get any comment at all [on the issue],” said Mr Salmond, in response to a question from US TV crews staying in Scotland for the referendum.
“A very prominent member of the United States government said to me it was the least he could say, given the requests that they’d had. I don’t think I, as First Minister of Scotland, have anything to teach the people of the United States of America about the benefits of securing independence from London.”
Meanwhile, MPs used the final Prime Minister’s Questions before the referendum to appeal to Scots to reject independence.
But a Westminster session dominated by the Scottish question also saw a backlash among English MPs over a pledge by the three UK party leaders to devolve more powers to Scotland.
Leader of the House William Hague took questions in Mr Cameron’s absence.
Mr Hague told MPs: “I hope the message the people of Scotland will hear from this House, where Scottish parliamentarians have made an immense contribution for generations, is that we want to stay together and we cannot imagine life on these isles without them.
“We are all proud to be British, combining these identities, and there is no doubt we would all be diminished if Scotland was separated from the people of the rest of the UK.”
Downing Street refused to comment on Mr Cameron’s political future, post-referendum.
A Westminster source said: “This is not about any one politician, or any one party, but about the future of five million people for decades to come.”