The harsh criticism comes after Romney's strong performance in Wednesday's debate, the first of three scheduled between the two men before Election Day.
Axelrod lauded Romney's "very good performance" but said the GOP hopeful's campaign is "completely unrooted in fact."
"He spent 90 minutes trying to undo two years of campaigning," Axelrod said.
He took specific umbrage with Romney's tax plan, which calls for lowering the corporate tax rate and closing associated loopholes to remain deficit-neutral. Romney has refused to say what loopholes specifically he would close.
"If you took away all the loopholes for upper-income Americans, every single one of them, he would still be trillions of dollars short."