A first-half brace from Lautaro Martinez sealed a 2-1 victory for the Nerazzurri, who had initially fell behind thanks to Nicolas Gonzalez's third-minute opener.
It marks a ninth Coppa Italia title for Inter, and means manager Simone Inzaghi now has three winners medals as a manager to go with the three he won as a player.
Vincenzo Italiano's side threw everything at Inter in the second half, but Inter were able to hang on despite intense pressure in the final 15 minutes.
Fiorentina were quick out the traps, something that viewers of Italian football have become accustomed to under the stewardship of Italiano, and they caught Inter out inside the first three minutes by taking an early lead.
After wrestling back possession midway inside Inter's half, Giacomo Bonaventura picked out Jonathan Ikone, and the Frenchman's dangerous low delivery found Gonzalez all on his own at the back post and the Argentine beat a sprawling Samir Handanovic to give La Viola the lead.
Inter looked to respond almost instantly and much of their threat was always likely to come from their wing-backs, with Denzel Dumfries' bombarding run setting up Edin Dzeko, but Gaetano Castrovilli got his body in the way crucially.
Reaching the midway point of the first half, Dzeko was presented with another glorious opportunity after Martinez outmuscled Nikola Milenkovic and played the Bosnian through, but he skied his effort with Fiorentina keeper Pietro Terracciano rushing out.
However, Inter would not have to wait long for another gilt-edged opportunity, and it all came after Francesco Acerbi was on hand to make a crucial challenge on Bonaventura who would have had a sighter on goal.
Instantly down the other end, Marcelo Brozovic's neat through ball found Martinez, who was kept onside by Milenkovic, and the Inter frontman finished clinically from a tight angle to score goal number 26 of the campaign, beating his tally from last season.
With the Nerazzurri taking control, they wasted no time in taking advantage of their territorial gains, and Martinez was sharper to reach Nicolo Barella's right-wing cross before Milenkovic to then fire home a phenomenal acrobatic volley, giving Terracciano no chance with the power on the strike.
Fiorentina struggled to really threaten the Inter goal intensely in the early stages of the second half, with Arthur Cabral and Gonzalez efforts both resulting in comfortable saves for Handanovic, but the game came to life as it entered the final quarter.
Romelu Lukaku made a positive impact after coming off the bench, initially stinging the palms of Terracciano with his first shot on goal.
The Belgian striker then showed off his creative abilities, as his square ball looked destined to be tucked away by fellow substitute Robin Gosens, but Dodo did enough to put the German off, as his effort skewed over the bar.
That opportunity kicked off a hectic few minutes of end-to-end action, as Luka Jovic was denied by a fantastic save from Handanovic after the Serbian had left two Inter defenders in his wake.
With Italiano committing more men forward, it left gaps at the back for Inter to penetrate but Inzaghi's side were wasteful on the counter, and were almost punished as Jovic squandered another brilliant chance when he headed wide from Dodo's cross.
The chances kept coming for La Viola, and it was no surprise that it came via Gonzalez, who, after leaving both Barella and Gosens on the floor, saw his dink cleared away from near the goalline by Matteo Darmian.
Jovic saw another effort flash agonisingly wide in stoppage time as it became apparent it was just not Fiorentina's night in the capital, as Inter were able to hold on for a 2-1 win, clinching a ninth Coppa Italia title.
Having garnered a reputation as cup specialist, Inzaghi has now won his seventh major honour as a manager, and fourth with Inter, holding onto the Coppa Italia crown they won last season.
For Italiano's side, they still have another cup final to look forward to when they face West Ham United in the Europa Conference League final in two weeks time, like Inter who will contest a European final of their own in the Champions League.
That will now be their only route back into Europe too, with a top seven finish now out of the question in Serie A for Fiorentina.
This success is the perfect preparation for Inter heading into the Champions League final against Manchester City next month, but their attention will soon turn back to the race for a top-four spot in Serie A.