Gordon Wilson said negative campaigning worked and SNP MSPs and MPs and cross-party allies in the Yes Scotland group should "be deployed as soon as possible in a managed offensive" against "the enemy" of the UK capital and the prosperous south of England.
His call came in what he described as a mid-term report card on the referendum battle, produced for the pro-independence Options for Scotland think-tank.
In a withering analysis, Mr Wilson gave the pro-independence side three marks out of 10 and the pro-UK side four.
He said Yes Scotland had campaigned with "all the excitement of a robot" and had allowed itself to become a "punch-bag," adding: "Political punch-bags do not usually win votes."
The former MP, who was succeeded as leader of the SNP by Alex Salmond in 1990, warned the Yes campaign had become "bogged down in trench warfare" about the currency, Europe and other issues that could not be resolved in detail until after a Yes vote.
However, his most controversial advice came over the future direction of the campaign.
Mr Wilson said voters should be offered additional referendums, if Scotland becomes independent, on the country's currency, joining the EU and retaining the monarchy, in a move he claimed would outflank the pro-UK campaign.
He urged pro-independence campaigners to mount an all-out attack on the "rapacious greed of southern England" which he accused of "gobbling up the wealth" at the expense of other parts of the UK.
"Scotland, with the moral support of the North, should strike at the southern cancer," he said.
Justifying a more determinedly negative tone than the SNP's "Westminster isn't working slogan," he added: "From Yes Scotland and the Government, there is the peculiar notion that negative politics does not work - something the Americans would find strange."
A spokesman for Yes Scotland said: "The Options for Scotland report is an interesting contribution to the debate. Gordon Wilson has suggestions for both campaigns, but I think we can be confident he will be voting Yes."
However, the report was condemned by Better Together and Scottish Labour. A Better Together spokesman said: "The language used in this report is nothing short of disgraceful.
"To talk of 'the cancer of the South' is completely ridiculous and totally out of tune with how people think in this country. The way that the nationalists talk about the rest of the UK and consistently blame every problem and every issue on someone else shows up their so-called positive campaign for the sham that it is."
Drew Smith, Labour's constitution spokesman, said: "This stinging rebuke to the separation campaign by a leading nationalist shows the underlying tensions within their campaign.
"Scots won't be convinced by a campaign that can't even answer the basic questions it is being asked."