Valencia took an early lead at the Emirates Stadium last week, but a double from Alexandre Lacazette and a late Pierre-Emerick Aubameyang effort have put the Gunners in control ahead of Thursday's meeting at the Mestalla.
Boss Marcelino deserves credit for getting Valencia into a position where they could qualify for next season's Champions League and win the Europa League, but Los Ches must perform over their next three games to achieve one of those targets.
Defeats to Atletico Madrid and Eibar in La Liga were followed by the setback in North London last Thursday, and it has put Marcelino's squad on the back foot ahead of welcoming the Premier League club.
Valencia returned to winning ways at the weekend with a 6-2 triumph at struggling Huesca, but it has done little to reassure supporters that their side can overturn a deficit under pressure later this week.
Marcelino has witnessed his defence perform solidly throughout the season, but Valencia are currently on a seven-game streak without a clean sheet in La Liga.
Just one shutout has been registered in their last five outings in Europe, and it will only provide Arsenal with encouragement as they attempt to score the two goals which would leave Valencia requiring an unlikely five to progress.
The biggest plus from the weekend was how Valencia maintained their strong start, something which they were unable to do when taking an early lead against Arsenal at the Emirates.
However, Valencia have now conceded last-minute goals in each of their last three matches in all competitions, and it is something which will undoubtedly concern Marcelino ahead of this contest.
Recent form: WWDWWL
Recent form (all competitions): WWLLLW
Opinion is currently divided over the success of Unai Emery's first year in charge at Arsenal, and it may take lifting the Europa League trophy for the Spaniard to win over any critics at the Emirates Stadium.
Arsenal had been in a position where achieving Champions League football through the Premier League was in their own hands, but just one point from four matches has led to the Gunners being highly unlikely to achieve a top-four position.
That run of form has placed increased priority on winning this competition, and Arsenal are the best placed out of the remaining four teams in the tournament to reach the final in Baku.
Emery will be worried about the number of chances which are being gifted to the opposition, but both Lacazette and Aubameyang have rediscovered their form in the final third.
The pair have contributed a combined total of seven goals and two assists from their last half-a-dozen outings, and improving on that in Spain on Thursday night will leave Arsenal on the brink of the final.
Arsenal suffered defeats at BATE Borisov and Rennes during the early knockout rounds, but recording a 1-0 win away at Napoli in the last eight has proven that the North London outfit can produce big performances on the road.
The English side found themselves making the trip to Spain at this stage of last season's competition, but a 1-0 setback at Atletico Madrid left the club missing out on another European final.
Much of this squad was present for the disappointment at the Wanda Metropolitano, and Emery will hope that lessons have been learned from that experience.
Recent form: LWLWWW
Recent form (all competitions): WLLLWD
Emery is likely to hand a recall to Laurent Koscielny after the centre-back sat out the game with Brighton & Hove Albion on Sunday.
Marcelino may opt to make minimal changes to the team which blitzed Huesca at the weekend, meaning that Valencia could start with a back four.
Valencia possible starting lineup:
Neto; Piccini, Gabriel, Garay, Gaya; Wass, Parejo, Coquelin, Guedes; Mina, Moreno
Arsenal possible starting lineup:
Cech; Mustafi, Sokratis, Koscielny; Maitland-Niles, Guendouzi, Xhaka, Kolasinac; Iwobi; Aubameyang, Lacazette
Head To Head
Thursday's fixture will represent the seventh competitive meeting between the clubs, with Valencia registering three wins in comparison to two victories for Arsenal.
Four of the previous games took place in the Champions League between 2001 and 2003, with Arsenal only prevailing on one of those occasions.
Arsenal have suffered defeat on each of their previous two visits to the Mestalla.
We say: Valencia 2-1 Arsenal
Valencia will fancy their chances of getting the better of Arsenal in Spain, but Arsenal showed against Napoli in the quarter-finals that they are capable of defending a lead away from home. We feel that the visitors will get on the scoresheet, and that could prove decisive come the full-time whistle.