Rudi Garcia's draw specialists held a slender edge over their Serie A counterparts after claiming a 1-1 scoreline in first leg of the last 16 tie but that was obliterated amid a shambolic first half display.
Gonzalo Rodriguez opened the scoring from the penalty spot and defensive errors allowed Marcos Alonso and Jose Basanta to put Fiorentina 3-0 up, effectively ending the tie after 22 minutes.
On the back of a 2-0 league reverse at home to Sampdoria over the weekend and having last witnessed a victory on home turf in November, the Roma support that remained in the ground after the early collapse made their displeasure clear.
The iconic Curva Sud became virtually deserted, as the club's ultras used their feet to display their anger.
Fiorentina, who were also winners at the Olimpico in the Coppa Italia last month, were left to reflect on a clinical evening's work and an 11th consecutive unbeaten away outing in Europe, while Adem Ljajic's late dismissal rubbed salt in Roma's painful wounds.
Roma's away-goals advantage was wiped out early on as Jose Holebas foolishly went through the back of Matias Fernandez in the seventh minute, leaving referee Cuneyt Cakir with little option other than to point to the spot.
The Turkish official ordered Rodriguez to retake after converting his initial effort due to encroachment - Basanta collecting a booking that will rule him out of the quarter-final first-leg during the ensuing protests - but the former Villarreal man kept his cool to send Skorupski the wrong way for a second time and open the scoring.
Roma chased the equaliser, but they soon fell further behind in farcical circumstances.
Skorupski rushed from his goal to stop a back-header from Vasilis Torosidis from going out of a corner, but in doing so palmed the ball the ball to Alonso, who dribbled towards an unguarded net to finish.
Basanta was then given ample room to plant home a header from Fernandez's right-wing corner and droves of Roma fans were streaming towards the exits.
Former Fiorentina man Ljajic led a futile bid for a home fightback, blasting at goalkeeper Neto from close range before curling over from outside the area and Borja Valero denied Roma a lifeline by clearing Miralem Pjanic's header from the goalmouth as home efforts became increasingly frantic.
Mohamed Salah hit the crossbar and post either side of Gervinho spurning a chance to tap into an open goal as the second half became more notable for the irate Roma fans blasting their team.
Ljajic's petty foul on the Egyptian earned him a late second yellow card to sum up a malaise and frustration surrounding Roma that does little for Garcia's long-term job prospects.
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