But standing in their way is former manager Unai Emery - sensationally dismissed as Gunners head coach in November 2019.
Taking over at a Villarreal side that finished fifth last season, he has them battling for a European berth again - and will be hoping to upset his former employers here.
Here, SPORTbible takes a look at everything you need to know ahead of the first leg of their Europa League semi-final.
How to watch Villarreal vs Arsenal
Villarreal vs Arsenal is scheduled for an 8pm (BST) kick-off on Thursday, April 29.
The match will be held behind closed doors at the Estadio de la Ceramica in Villarreal, Spain.
It will be televised on BT Sport 3 from 7.15pm.
Regular subscribers can also stream matches via the BT Sport website or BT Sport app on a variety of devices including laptops, smartphones and tablets.
Villarreal vs Arsenal predictions and betting odds
Arsenal's goalscoring exploits on the road in recent weeks have been admirable, and they will endeavour to keep that streak going now that Pierre-Emerick Aubameyang and Alexandre Lacazette are back in the fold.
But Villarreal's Emery knows a thing or two about Europa League triumphs and the ex-Arsenal boss will surely be dreaming about dumping his former employers out of the tournament.
The Spaniard has reinvigorated his managerial career with Villarreal, who have won 11 out of their 12 Europa League games this season so far - including a perfect record of six wins from six at home.
With that said, though, Arsenal are unbeaten in four meetings with Villarreal since 2005 - winning two and drawing two against the La Liga powerhouses.
The Gunners look like they have with it takes to come away with at least a draw and set up a nail-biting second leg at the Emirates.
Villarreal are 29/20 to win, with Arsenal priced at 19/10 to come away with the victory. A draw is priced at 12/5.
Odds are correct at the time of publication and are subject to change.
Villarreal team news and injuries
Villarreal manager Emery is likely to have almost a full squad to choose from.
Manu Trigueros received his marching orders in the loss to the Blaugrana, but is free to start here.
Arsenal team news and injuries
Arsenal could welcome back captain Aubameyang back into the side after missing the last four games due to contracting malaria.
In another major boost for the Gunners, Arteta revealed that Lacazette, who has overcome a hamstring complaint, as well as Kieran Tierney, could all make Thursday's game.
However, Arteta is known to be cautious when integrating players back into the team, so the fit-again quartet will hope to make an impact from the bench, unless the Spaniard decides to risk them from the off.