Manager Unai Emery is also looking to achieve European glory in each of his three seasons in charge of the Andalusian club -- another potential first.
Liverpool has won the competition three times in its old guise as the UEFA Cup, and will be vying for its first European trophy since 2005's historic come-from-behind victory against AC Milan in the Champions League final.
Shades of 2005 echo in this match for Liverpool, which finished fifth in the English Premier League in its first year under Rafa Benitez.
This season's crop are coached by Jurgen Klopp, who's looking to secure a cup victory despite taking over mid-season at Anfield.
"The bigger the pressure, the cooler I get," the German recently told UEFA
. "I know it's not about forcing it with all you have; it's about the game.
"The game works with joy, with confidence, with working together and dreaming together ahead of the game, and doing everything to make the dream come true with the work you do on the pitch. Nothing is guaranteed but everything is possible."
Form: Neither team has set the world on fire in their respective leagues. Sevilla finished seventh in La Liga, ensuring a return to the competition even if Wednesday ends in defeat.
Liverpool, however, finished eighth in the Premier League, meaning victory is the Reds' only hope of playing in Europe next season.
In the last few weeks Liverpool's form has been mixed, with two wins, two draws and two losses in the past six matches, though that did include a convincing 3-0 home win against Villarreal in the second leg of the Europa League semifinal.
Klopp is hoping to shake off a run of bad form in cup finals, losing four in a row between his stints at Borussia Dortmund and Liverpool. That includes the 2013 Champions League final against Bayern Munich and this season's League Cup final loss to Manchester City.
Sevilla's form has been equally variable, with two wins, three losses and one draw in the last six games -- though one of those victories was the 3-1 win over Shakhtar Donetsk at home in the second leg of their Europa semifinal.
"Coaches and players know that this is a job in which you find enjoyment by struggling to overcome an opponent. It's a battle, and obviously at times it's not very pleasant ... when it's a very evenly-matched, fiercely-contested fight, that's when it becomes about enjoyment through pain.
Who to watch: For Sevilla, all eyes will be on French striker Kevin Gameiro, who has netted seven of the team's 14 goals in the Europa League, while contributing one assist. Captain Jose Antonio Reyes (appendix) and Michael Krohn-Dehli (knee) are out.
Liverpool's Brazilian talisman Philippe Coutinho has contributed two goals in the Europa League, as did England striker Daniel Sturridge, while Adam Lallana led their European campaign with three goals.
Captain Jordan Henderson is one match back from a knee injury, while young Belgium forward Divock Origi might feature after recovering from an ankle injury. Defender Mamadou Sakho is suspended pending a drug investigation.
Champions League implications: If Liverpool wins it will join Premier League champion Leicester City, Arsenal, Tottenham and Manchester City in Europe's top competition.
If Sevilla triumphs it will join champion Barcelona, Real Madrid, Atletico Madrid and Villarreal for another crack at the ultimate prize.
Just being in the group stage is worth €12 million ($13.5 million) for each team, with an extra €1.5 million ($1.7 million) for a win and €500,000 ($566,000) for a draw, plus a share of the overall prize pool.