In a statement to CNN, Petraeus said some members of the al Qaeda affiliated al Nusra Front might be persuaded to join the coalition battling the IS group.
Read: Islamic State listed among proscribed outfits
"We should under no circumstances try to use or co-opt Nusra, an al Qaeda affiliate in Syria, as an organisation against ISIL," Petraeus told CNN, using another acronym for the IS group.
"But some individual fighters, and perhaps some elements, within Nusra today have undoubtedly joined for opportunistic rather than ideological reasons: they saw Nusra as a strong horse, and they haven't seen a credible alternative, as the moderate opposition has yet to be adequately resourced."
So, Petraeus argued, it may eventually be possible to "peel off so-called 'reconcilables' who would be willing to renounce Nusra and align with the moderate opposition to fight against Nusra, ISIL, and (Syrian President Bashar al Assad.)"
Petraeus became a household name in the United States when he oversaw the troop "surge" in Iraq in 2007, and US leaders credited him for salvaging the troubled war effort.
Part of that operation saw the decorated general convince Sunni fighters to stop fighting with al Qaeda and to work with the US military.
His statement Tuesday followed the publication of a story in the Daily Beast that pointed out the irony of the United States working with anyone connected to al Qaeda, which carried out the September 11, 2001 attacks and triggered America's so-called war on terror.
Read: Countering Islamic State: Al Qaeda's Zawahiri pledges allegiance to new Taliban chief
The Daily Beast said several officials it had spoken to found Petraeus's idea to be politically toxic, almost impossible to carry out and strategically risky.
In his statement to CNN, Petraeus said using any Nusra fighters would require "both the rise of much stronger, moderate opposition groups -- backed, again, by the US and the coalition seeking to defeat ISIL -- and at the same time, intensified military pressure on all extremist groups."
Petraeus, 62, had a spectacular fall from grace this year when he pleaded guilty to providing classified secrets to his mistress. He was given two years' probation and a $100,000 fine.
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