The Spanish side won the 2013-14 final against Benfica on penalties, lifting the trophy for the third time in nine years.
However, they were dealt a difficult route to the knockout stages at Friday's draw in Monaco, landing in Group G alongside Stadard Liege of Belgium, the Netherlands' Feyenoord and Croatian outfit Rijeka.
No club has won Europe's second-tier club competition more than Inter, and the Italian giants will not be daunted by their opposition in Group F.
Walter Mazzarri's men have been drawn to face Dnipro, Saint-Etienne and Qarabag.
Group H looks set to be one of the most hotly contested in the competition as Ligue 1 outfit Lille, who missed out on a spot in the UEFA Champions League to Porto, come up against Wolfsburg, Everton and Krasnodar.
Napoli also missed out on a place among Europe's elite after tasting defeat against Athletic Bilbao in the play-offs earlier this week, but will now turn their focus to bettering last season's Europa League display.
Rafael Benitez's men reached the last 16 in 2013-14, and face Sparta Prague, Young Boys and Slovan Bratislava in Group I this time around.
Mauricio Pochettino's first European campaign in the Tottenham hotseat takes him to Besiktas, Partizan and Asteras Tripolis in Group B, while Villarreal face Borussia Monchengladbach, Zurich and Apollon.
Rio Ave's first appearance in the competition will see them clock up some air miles with trips to Dynamo Kiev, Steaua Bucharest and Aalborg in Group J.
Group B contains Copenhagen, Club Brugge, Torino and HJK, while Salzburg, Celtic, Dinamo Zagreb and Astra will do battle in Group D.
Fiorentina headline Group K, which is also home to PAOK, Guingamp and Dinamo Minsk, and Group L could be wide open with Metalist, Trabzonspor, Legia Warsaw and Lokeren involved.
In the remaining group – Group E - PSV face Panathinaikos, Estoril and Dinamo Moscow.
Full draw for the 2014-15 UEFA Europa League group phase:
Group A - Villarreal, Borussia Monchengladbach, Zurich, Apollon
Group B - Copenhagen, Club Brugge, Torino, HJK
Group C - Tottenham, Besiktas, Partizan, Asteras Tripolis
Group D - Salzburg, Celtic, Dinamo Zagreb, Astra
Group E - PSV, Panathinaikos, Estoril, Dinamo Moscow
Group F - Inter, Dnipro, Saint-Etienne, Qarabag
Group G - Sevilla, Standard Liege, Feyenoord, Rijeka
Group H - Lille, Wolfsburg, Everton, Krasnodar
Group I - Napoli, Sparta Prague, Young Boys, Slovan Bratislava
Group J - Dynamo Kiev, Steaua Bucharest, Rio Ave, Aab.
Group K - Fiorentina, PAOK, Guingamp, Dinamo Minsk
Group L - Metalist, Trabzonspor, Legia Warsaw, Lokeren
