Having battled out a goalless draw in London in the opening leg of the last-16 clash, the match appeared to be heading for extra time when Spain international Fabregas smashed in a brilliant 25-yard strike with just six minutes left.
Emmanuel Adebayor then added a second in stoppage-time as Arsenal became the first English side to beat Milan on their own patch.
Barcelona also progressed thanks to a 1-0 defeat of Celtic at the Nou Camp.
The Catalan club had led 3-2 from the first match in Glasgow and Xavi's goal after three minutes effectively ended any hopes of a Celtic comeback.
Gordon Strachan's men did well to contain Barca's superstars for the rest of the game but the home side cruised into the last eight on a 4-2 aggregate success.
Cristiano Ronaldo again showed his liking for the big stage by scoring the only goal at Old Trafford as Manchester United overcame French champions Lyon.
The Portugal winger steered the club to a 10th straight home victory in the competition, equalling Juventus' record set 11 years ago.
Ronaldo struck in the 41st minute to break Lyon's resistance and secure a place in the quarter-finals with a 2-1 aggregate win.
In Tuesday's other last-16 clash, Volkan Demirel was the hero for Fenerbahce as they advanced from a penalty shoot-out into the quarter-finals for the first time in their history.
After 90 minutes Sevilla led 3-2 to cancel out the first-leg deficit and make the scores 5-5 on aggregate, and with no goals in extra time it was left to visiting goalkeeper Volkan, who saved from Julien Escude, Ivica Dragutinovic and Dani Alves.
Volkan had earlier gifted Sevilla a two-goal lead within nine minutes after failing to deal with long-range efforts from Dani Alves and Seydou Keita.
Brazilian forward Deivid then pulled a goal back for Fenerbahce on 20 minutes, but Sevilla restored a two-goal advantage with a deflected Frederic Kanoute shot just before half time.
Deivid pounced for his second with 11 minutes left, and with no more goals after extra time it was left to Volkan to make amends for his earlier errors.
He saved Sevilla's second penalty from Escude, and although Palop kept out Edu Dracena's powerful effort in response, Volkan then stopped Enzo Moresca's blasted shot and punched away Alves' powerful effort to send the Turkish side through.
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