A brace apiece from Bruno Fernandes and Edinson Cavani, coupled with goals from Paul Pogba and Mason Greenwood, secured Manchester United an emphatic victory that all but assures their place in the final.
Lorenzo Pellegrini and Edin Dzeko scored in the first half to cancel out Manchester United's early opener. But a spectacular collapse in the second half have all but extinguished AS Romas' hopes of reaching the final.
Despite scoring two away goals, the Giallorossi face an uphill task in the second leg to mount an improbable comeback.
On that note, let's have a look at the player ratings of both teams.
David de Gea - 6/10
David de Gea wasn't at fault for either of AS Roma's goals and couldn't have done anything about them. He made one mistake by passing straight to Dzeko but made up for that almost instantly by getting a hand to the Bosnian's effort.
Aaron Wan-Bissaka - 6/10
Aaron Wan-Bissaka was regularly caught out on the break but made up for that with an excellent attacking game, linking up brilliantly with Marcus Rashford.
Viktor Lindelof - 6/10
Viktor Lindelof was crucial to building from the back for Manchester United but left a lot to be desired in marking his opposite numbers. He also lacked positional awareness on the night.
Harry Maguire - 6/10
Harry Maguire struggled with Edin Dzeko's pace and was beaten by the Bosnian in the air for AS Roma's second goal too. The Manchester United captain improved after the break and got himself involved in the attack.
Luke Shaw - 6.5/10
Luke Shaw was largely quiet in the first half, but, like many of his Manchester United teammates, he burst into life in the second, overlapping brilliantly and providing some good crosses.
Scott McTominay - 6/10
Scott McTominay kept close to Mkhitaryan, who beat him once with a defence-splitting pass that led to Dzeko's goal. But McTominay kept the Armenian under wraps in the second half.
Fred - 5/10
On a night when Manchester United got everything right, Fred didn't. The Brazilian looked pale in comparison to his teammates and came a cropper defensively too.
Marcus Rashford - 7/10
Amidst the flurry of goals, Marcus Rashford worked hard to get the ball around but failed to get on target himself.
Bruno Fernandes - 8/10
For all the chatter about him not performing in big games, Bruno Fernandes walked off with two goals and two assists on the night, producing another vintage display for Manchester United.
Paul Pogba - 7/10
Paul Pogba was involved in Manchester United's opening goal and then conceded a penalty. But the Frenchman recovered by linking up with Fernandes to devastating effect. In an impressive outing, Pogba also provided Fernandes with a sublime cross to make it 5-2 for Manchester United on the night.
Edinson Cavani - 8/10
El Matador also struck twice - one was a lovely finish, while the other came after he pounced on a mistake from the AS Roma goalkeeper. Edinson Cavani capped off a superb performance with a deft assist for Fernandes. Do Manchester United need any more reason to extend his contract?
Ratings of Manchester United Substitutes:
Mason Greenwood - 7/10
The Manchester United youngster added the finishing touches to a glossy win with a sublime goal to make it six, bringing his season tally in all competitions to nine.
Nemanja Matic - 6/10
Nemanja Matic came on in the 86th minute but looked anonymous.
Juan Mata - N/A
Juan Mata didn't see much of the ball, as he came on too late.