The Bluebirds had fallen behind just before the half-hour thanks to an excellent finish from Daryl Murphy, but Whittingham levelled matters eight minutes later with a brilliant effort from 30 yards that flew into the top corner.
Cardiff never looked back, with further goals from Macheda and Le Fondre making it two wins out of two for Slade and ending Ipswich’s eight-match unbeaten run.
Slade could be forgiven for thinking Championship management has proved easier than he had expected, but the opening half an hour was far from straightforward for his side.
The Tractor Boys had the best player on the park in on-loan Crystal Palace midfielder Jonathan Williams, and he tormented the Bluebirds with his incisive play.
After Anthony Pilkington’s dipping shot was tipped over the Ipswich bar by Dean Gerken, Williams took over.
The Wales international’s driving run through the heart of midfield put the home side in reverse, but Conor Sammon did not make the best use of his efforts as he fired across the face of goal.
Williams then himself fired wide after he had found space to receive Tyrone Mings’ pass on the edge of the Cardiff area.
But when Ipswich’s opener came, it was down to an error from Fabio rather than brilliance from Williams.
The full-back had been forced to miss the weekend win over Forest through illness, and Slade could have been forgiven for wishing he was still on his sickbed when he failed to cut out Jonathan Parr’s pass, allowing Murphy to drive forward and hit an unstoppable drive beyond David Marshall.
It was Murphy’s seventh goal of the season, but his stunning strike was bettered just eight minutes later by Whittingham.
Ipswich failed to clear a cross and Whittingham picked up the loose ball, took aim and dispatched a shot into the top corner from fully 30 yards.
The strike rocked Ipswich, and it appeared they still had not recovered when they fell behind just two minutes into the second half.
Full-backs Mings and Parr were guilty of failing to deal with balls into the box, and when Pilkington blazed a volley cross the six-yard box, Macheda was on hand to tap in.
Cardiff sensed the visitors’ vulnerability and pushed forward in search of a third, with Gerken denying Fabio at close range and then making a diving stop from Craig Noone’s curling effort.
The Tractor Boys had a good chance of their own, with Murphy’s far-post header dropping agonisingly wide of the upright.
The miss proved costly as Cardiff went up the other end to clinch the three points.
Sean Morrison’s header dropped to Le Fondre and the former Reading man’s low left-foot shot found its way in via the inside of the post.
David McGoldrick and Cole Skuse had half chances to trim Cardiff’s lead and set up a nervous finale, but David Marshall was more than equal to their efforts.