Andrea Stramaccioni's men managed to triumph in Milan at long last, with this overdue victory in their own backyard propelling them into third place
Diego Milito opened the scoring from the penalty spot before strike partner Antonio Cassano doubled the Nerazzurri's advantage on 34 minutes.
Romulo netted just before the break to drag the Viola back into the game but Gonzalo Rodriguez's dismissal for a second bookable offence on the hour mark ended the visitors' hopes of denying Inter a first home win of the season.
Andrea Stramaccioni sent out the same three-man backline that served him well against Chievo earlier during the week, the Nerazzurri's formation mirroring the 3-5-2 formation sent out by their visitors.
Philippe Coutinho, handed a rare start in place of regular playmaker Wesley Sneijder, really relished his chance to shine early on, with some promising link-up play down the left with Yuto Nagatomo allowing the Brazilian to deliver Inter's first ball of the night into the Viola box, only for Facundo Roncaglia to intervene.
Cassano also began brightly, bombing down the left flank to create an opening for Coutinho, although Rodriguez stood strong in the middle to intercept. The latter was to go from hero to villain shortly after, though, as a cross from compatriot Javier Zanetti came off his arm, leaving referee Antonio Giannoccaro with no choice but to point to the spot.
Evergreen striker Milito stepped up to bury the ball into the bottom left corner of the net with aplomb, sparking wild celebrations from Zanetti and Co. The goal visibly eased the home side's nerves, as Inter began looking increasingly likely to seize on the mistakes made by Fiorentina's creaking defence.
Viola talisman Stevan Jovetic kept opposing custodian Samir Handanovic on his toes with a free kick that came off the post in the 21st minute but, for the most part, it was one-way traffic in the direction of the Fiorentina goal, which was summed up by Milito conspiring to miss not one, but two, easy chances to double his team's lead.
The 33-year-old flicked a searching Cassano pass over the head of Roncaglia only to volley against the crossbar, and then had the San Siro faithful gasping in disbelief as he fired straight at the imposing Emiliano Viviano, after being slipped through one-on-one by his fellow forward.
Cassano ensured his team-mates would not have to wait long for a second goal, though, as his 90th Serie A strike, and fourth in his five Nerazzurri appearances, sparked emphatic cheers from onlooking spectators. A beautifully-executed dummy from midfield lynchpin Esteban Cambiasso allowed the ball to roll across to the Barese, who made no mistake by wrong-footing Viviano from close range.
A fine header from Romulo in the 41st minute, after a David Pizzaro cross, could not distract from the fact the season's surprise package had been comprehensively outplayed in the opening half. Fiorentina boss Vincenzo Montella knew as much, and he elected to introduce Matias Fernandez in place of the ineffective Adem Ljajic as a result.
The substitution appeared to galvanise the visitors, as they controlled the opening minutes of the second period. However, a silly second booking on the part of Rodriguez, for a clumsy challenge on Nagatomo, undid all of the visitors' good work.
Milito missed another sitter after heading a cross straight at Viviano from six yards out, as Inter began shoring up their lead with the introduction of workhorse Gaby Mudingayi. As Fiorentina started to run out of steam following the sending-off, the match slowed to walking pace, with Inter reluctant to take any risks going forward, and their opponents unable to summon up the energy for a grandstand finish.
Consequently, the hosts were able to coast to a victory that lifts them to third, just four points behind front-runners Juventus and Napoli, while Fiorentina remain eighth.