The Gunners cruised through the group stage but have made hard work of their two knockout-stage fixtures thus far, while Napoli travel to London for this first leg on the back of wins over also-rans FC Zurich and Red Bull Salzburg.
Unai Emery's debut campaign in English football can still go one of two ways as we approach the final weeks of the season. The Gunners remain on course for a top-four finish in the Premier League and Europa League glory, though that can all change in an instant.
After steadily building momentum for a number of weeks, culminating in a convincing 2-0 win over Newcastle United last week to extend their winning league run on home soil to 10 matches, Arsenal came crashing back down to earth with a 1-0 loss to Everton on Sunday.
On a weekend when top-four rivals Manchester United and Tottenham Hotspur were not in action, with the Champions League instead taking priority for them, the Gunners blew their chance to consolidate their place in the top four.
Instead, Chelsea's 2-0 triumph at home to West Ham United on Monday leaves Emery's men in fifth place and with plenty of work still to do if they are to reach the Champions League via the traditional league route.
Should Arsenal finish lower than fifth, they will only have their away form to blame. At home they have been very impressive this term, winning 14 and drawing two of their 17 league matches at the Emirates Stadium, including that ongoing 10-match winning streak.
It is not just domestically that Arsenal have looked poor on their travels, though, as they crashed to first-leg defeats at BATE Borisov and Rennes in the Europa League last 32 and last 16 respectively, before recovering with victories on home soil.
Against Rennes, meanwhile, a side sitting in the bottom half of Ligue 1 at the time, Arsenal threw away a one-goal advantage to lose the first leg 3-1 in France. Again, they looked a completely different side in the reverse fixture and progressed 4-3 on aggregate.
Arsenal have been beaten just once in their last 17 home games in the UEFA Cup/Europa League, with their only defeat in that run coming against Ostersunds FK in the last 32 in 2017-18.
With home advantage in the first leg of this quarter-final tie, Emery's side cannot afford to travel to the Stadio San Paolo requiring a victory if they are to match - or indeed better - their semi-final finish of last season.
Recent form in Europa League: WWLWLW
Recent form (all competitions): DLWWWL
Napoli had aspirations of making it far in the Champions League at the start of the season, only to be dealt a tricky hand in the group phase.
The Partenopei were drawn in a group with heavyweight sides Paris Saint-Germain and Liverpool, as well as Red Star Belgrade, and could only manage a third-placed finish, despite losing just one match.
That loss came at Anfield in December in what was essentially a straight shootout for qualification to the knockout stages of the Champions League. Even accounting for that 1-0 reverse, Napoli finished with nine points - five of those coming against Liverpool and PSG - making them the best third-placed side in the group stage.
Napoli did not make life easy for themselves in that most recent European fixture as, after opening the scoring early on in Austria to make it 4-0 on aggregate, they conceded three times to leave the door open for their opponents.
That win means the Italian side have reached the quarter-finals of the UEFA Cup/Europa League for the third time in their history. They fell at the semi-final stage in 2014-15 but won the competition in 1988-89 with a side featuring Diego Maradona.
Ancelotti's side are not in the best of form ahead of this captivating Anglo-Italian affair, though, as they lost 2-1 at Empoli last week and followed that up with a 1-1 home draw against Genoa on Sunday, leaving them 20 points adrift of runaway Serie A leaders Juventus.
Challenging for the title, as they did under Maurizio Sarri last season, was always going to be difficult for Ancelotti in his first campaign at the Stadio San Paolo.
Matching 2017-18's second-placed finish and winning the Europa League would make this a superb season for the veteran coach, though. To achieve that, the Partenopei may have to do something they have not managed before: win away to an English side in European competition.
Recent form in Europa League: WWWL
Recent form (all competitions): DLWWLD
Sokratis Papastathopoulos is back from suspension for Arsenal after missing the second leg against Rennes and, given that he is now banned for two domestic matches, he seems certain to start this one.
Elsewhere, Amadou Diawara and Raul Albiol are carrying injuries and David Ospina - on loan from Arsenal but eligible to play against his parent club - is also expected to miss out because of a head injury suffered last month.
Arsenal possible starting lineup:
Leno; Mustafi, Sokratis, Monreal; Maitland-Niles, Ramsey, Guendouzi, Kolasinac; Iwobi; Aubameyang, Lacazette
Napoli possible starting lineup:
Meret; Malcuit, Maksimovic, Koulibaly, Rui; Callejon, Allan, Fabian Ruiz, Zielinski; Imsigne, Mertens
Head To Head
Arsenal and Napoli have met just twice before in Europe, both games coming in the 2013-14 season.
The Gunners won 2-0 at the Emirates Stadium in the group stage of the Champions League, before losing by the same scoreline at the Stadio San Paolo.
Napoli have lost seven and drawn one of their previous eight away matches against English opposition, going down to Burnley, Leeds United, Liverpool, Chelsea, Manchester City and indeed Arsenal.
We say: Arsenal 2-1 Napoli
Arsenal, quite simply, need a lead to take into next week's second leg in Italy. The Gunners have been terrible on their travels all season, in complete contrast to their home form. Playing the second leg on home soil would have worked out better for the Londoners, but Emery's side should at least pick up victory in Thursday's match.