Edinson Cavani was at his unplayable best as he scored twice and set up a number of others, while Bruno Fernandes (two), Paul Pogba and Mason Greenwood joined the ex-Napoli forward on the scoresheet. For Roma, a Lorenzo Pellegrini penalty and an Edin Dzeko strike had given them hope in the first half.
The Italians were unfortunate on the night and were forced into three substitutions in the first half through injury, leaving them without any more changes to make in the second half, having not taken the option to use their remaining two at half time.
United, though, were lethal and unforgiving in attack, and got up and running as early as the ninth minute when Bruno Fernandes. Paul Pogba had picked out Edinson Cavani and the Uruguayan laid off for the Portuguese to lift over Pau Lopez.
The lead lasted just six minutes though. Pogba handled a Rick Karsdorp cross, allowing Lorenzo Pellegrini to convert from the penalty spot.
Pellegrini turned provider as Edin Dzeko tapped in to give the Serie A side the lead, but their concerns only grew as Leonardo Spinazzola had to hobble off before the break. Although Paulo Fonseca had five substitutions to make, the rules state that those changes must be made in no more than three in-play breaks, meaning that his next two changes would have to come at half time or never.
With no changes made at the break, Roma saw their lead slip within three minutes of the restart. A nice move led to Bruno Fernandez finding Cavani who tucked an excellent finish into the top corner.
?From there, there was only one team likely to come out on top. Cavani got his second of the night as he tapped in from inside the six-yard box after Mirante had parried a shot into his path.
United had a penalty seven minutes later. Cavani, who had missed the ball at the near post, collided with Chris Smalling and Fernandes stepped up to convert for his second goal of the game.
Pogba headed in a Fernandes corner to make it five, before Cavani beautifully set up substitute Mason Greenwood to add a sixth.