Their unlikely triumph at the San Siro was a much-needed boost for Arsene Wenger's Gunners in an otherwise disappointing season, which now hinges on winning this competition.
Wenger's Gunners travelled to Italy on a four-game losing streak, a run of form which saw calls from the Frenchman's head grow to a deafening pitch, but their performance in the away leg was the ideal response to the naysayers.
The North Londoners have since built on their first-leg victory by returning to winning ways in the Premier League, defeating Watford by a convincing three goals to nil at the Emirates Stadium to move within 10 points of the division's top four.
Although it hasn't been the greatest of campaigns for Arsenal, their fans have cause to be confident that they will see the job through against Milan. The Gunners have been consistent at home this season, winning 11 out of their 15 league games at the Emirates and losing only twice.
In the Europa League, they have been clinical, winning four out of their six group matches to finish top of the pile in Group H, ahead of Red Star Belgrade, FC Koln and BATE Borisov.
They scored 14 times and conceded just four along the way for a goal difference of plus 10, a figure only bettered by Zenit St Petersburg and Real Sociedad.
Arsenal were equally clinical while dispatching Swedish outfit Ostersunds of Sweden 3-0 away from home, although their 2-1 defeat in the return leg seemed to trigger a dismal run of form.
Those two defeats to Manchester City - the first of which saw them miss out on the EFL Cup - that followed and the 2-1 reverse at Brighton & Hove Albion that came after that will continue to weigh heavy on Wenger and his players, but the signs that the Gunners have turned a corner are undeniable.
Most Arsenal fans were aggrieved that their team was playing in the Europa League at the beginning of the campaign. Now, the tournament represents their only hope of salvaging anything from a troubled season.
Recent Europa League form: DLWWLW
Recent form (all competitions): LLLLWW
Things were really looking up for Milan - and they were even installed as the bookmakers' favourites to win the Europa League - until the Gunners travelled to the San Siro and dealt their season a potentially-crippling blow.
The Rossoneri were on an impressive 13-match unbeaten run under coach Gennaro Gattuso, who has helped them make a near-flawless start to 2018.
Since Christmas, Milan picked up nine wins and four draws ahead of their showdown with the Gunners, and they have since returned to form in Serie A, beating Genoa away with the help of a stoppage-time strike from Andre Silva at the weekend.
While travelling to the Emirates with a 2-0 deficit to overturn sounds like a tall order, Milan fans have reason to believe it isn't quite mission impossible.
Solid away form under Gattuso has been the key to their recent revival, with the Italian giants winning all of their last four matches on the road, scoring 10 times and conceding none in the process.
The Rossoneri's overall form in the Europa League has been strong, as their last 20 fixtures at this level have seen them win 16 times, draw three and lose only once, a run which dates back to the days of the UEFA Cup.
That said, Milan haven't fared too well in last-16 European contests of late, winning just once in their last six attempts, although all of those ties came in the Champions League.
Arsenal, in fact, were the last team they defeated at this stage in a continental tournament, that two-legged victory coming in 2011-12 when they hammered the Gunners 7-0 on aggregate. That's the kind of clinical finishing they will have to display to stand any chance of overturning that two-goal deficit at the Emirates.
Recent Europa League form: DWLWWL
Recent form (all competitions): WWWWLW
Mesut Ozil, meanwhile, is likely to line up in the Gunners midfield despite picking up a minor knock.
Wenger has one fresh injury concern in the wake of the win against Watford, with Shkodran Mustafi suffering a groin strain against the Hornets, ruling him out of the Milan clash.
The visitors will have the same squad from the first leg at their disposal. Full-back Davide Calabria was their only injury concern, but he is expected to be fit for the trip to England having been rested against Genoa.
Arsenal possible starting lineup:
Ospina; Chambers, Monreal, Koscielny, Kolasinac; Xhaka, Wilshere; Ozil, Ramsey, Mkhitaryan; Welbeck
AC Milan possible starting lineup:
Donnarumma; Rodriguez, Romagnoli, Bonucci, Calabria; Kessie, Biglia; Bonaventura, Suso, Calhanoglu; Cutrone
Head To Head
Arsenal became the first team to beat Milan at the San Siro since 2002 when they saw off the Italians last week, but their overall fortunes against the Serie A outfit have been mixed.
The two sides have met twice in the Champions League, with Arsenal holding Milan to a goalless draw at home before defeating them 2-0 away to progress to the quarter-finals of the 2007-08 tournament.
They met again in the 2011-12 competition, and that's when the Rossoneri pulled off that resounding 7-0 aggregate victory to get their revenge on Wenger's men.
The only other competitive fixture between the two sides came in the 1995 Super Cup, when the Gunners drew 0-0 at home and won 2-0 at the San Siro to get their hands on the trophy.
We say: Arsenal 1-1 AC Milan
Although Milan have been in good form since the turn of the year, they were poor against Arsenal and their shortcomings were easy to see. The Italian giants have ground out most of their recent victories, struggling for goals and relying on a usually watertight defence. Since that backline came undone at the San Siro last week, they will need to abandon their usual gameplan and take the match to the Gunners.
Arsenal's troubles are also well documented, but positives results in their last two matches suggests they have turned a corner and will have restored some much-needed confidence at the Emirates, putting them in good stead to get the result they need to qualify for their first European quarter-final since 2009-10.