Two goals apiece from Adem Ljajic and Stevan Jovetic earned the Viola all three points in arguably their most impressive performance of the season.
Vincenzo Montella's side gave Inter no chance at all in a totally one-sided game, although Antonio Cassano did restore some pride for Inter with a fine consolation goal in the 86th minute.
That was not enough to prevent Inter from ending the weekend behind their city rivals AC Milan, who they meet in the second Derby della Madonnina of the season next Sunday.
It was clear Fiorentina were up for the task when Jovetic forced an excellent save out of Samir Handanovic in the third minute.
Ten minutes later, Ljajic beat Handanovic with a header into the top corner after Jovetic had flicked Manuel Pasqual's cross on to him.
Handanovic denied Jovetic again four minutes later, but the Montenegrin left him no chance with his 10th goal of the season in the 33rd minute, unleashing an unstoppable shot into the top corner from 20 yards.
Borja Valero was the next to test Handanovic, who also denied Alberto Aquilani as Fiorentina tore Inter apart.
A neat backheeled pass from Aquilani set up Jovetic for his second and Fiorentina's third 10 minutes into the second half.
Ten minutes later, Ljajic rubbed further salt into Inter's wounds with a curling effort from just outside the penalty area which Handanovic could only watch as it flew past him.
The last word belonged to Cassano, though, who restored some personal pride with the best goal of the night, and the previous four took some topping.
The Italy striker took aim from over 35 yards out and curled a shot in off the left-hand post, but not even that could bring a smile to his face as the heavy defeat saw him in no mood to celebrate.