Manchester United and last year's finalists Arsenal headline an English trio that also features Europa League newcomers Wolves while record five-time champions Sevilla figure to be among the primary contenders as the group stage begins Thursday.
Scottish rivals Celtic and Rangers face testing paths to the knockout rounds as bitter foes Roma and Lazio bid to end Italy's two-decade wait for the title.
Porto, PSV Eindhoven and Feyenoord are the other former European Cup winners in a competition that will welcome the eight third-place finishers from the Champions League groups for the knockout phase.
United, Europa League winners in 2017, will host Astana in Group L as Ole Gunnar Solskjaer's side face opponents from Kazakhstan for the first time in club history.
They will expected to progress with relative ease from a group that also includes Partizan Belgrade and former finalists AZ Alkmaar of the Netherlands.
Unai Emery's Arsenal return to the competition after last season's 4-1 defeat by Chelsea in the final in Baku saw the Blues pip them to Champions League qualification.
The Gunners visit Eintracht Frankfurt to kick off their campaign, with 10-time Belgian champions Standard Liege and Portugal's Vitoria Guimaraes also in Group F.
Wolves, in their first European campaign since 1980, will meet Portuguese club Braga in their opening game at Molineux.
Nuno Espirito Santo's team came through three ties just to reach the group stage. They beat Torino 5-3 on aggregate in the play-offs.
"I think any team in the Europa League are a good team who we will respect going up against them. We will give everything, try to play and try to beat any team," said Wolves winger Adama Traore.
"Any player wants to play in Europe, but the Europa League is exciting, it is a new thing for us and it's a good thing."
- Six newcomers -
Scottish champions Celtic travel to French Cup holders Rennes in Group E, with Italian Cup holders Lazio and CFR Cluj, the Romanian side to whom they lost in Champions League qualifying, completing a tricky section.
Steven Gerrard's Rangers are at home to Jaap Stam's Feyenoord on Thursday and will do well to navigate a group with Porto and Swiss champions Young Boys.
Roma will take on Istanbul Basaksehir in their first game while Moenchengladbach host Austria's Wolfsberg -- not to be confused with German outfit Wolfsburg.
Austria boast two representatives with LASK Linz among the six debutants -- alongside Espanyol, Wolves, Wolfsberg, Olexandriya and Ferencvaros -- in the tournament.
UEFA will distribute 560 million euros to clubs competing in this season's Europa League, just over a quarter of the 1.95 billion euros allocated to those participating in the Champions League.
Each of the 48 clubs in the group stage will receive a base of 2.92 million euros, with lifting the trophy worth just under 18 million euros in basic prize money.
Teams will net 570,000 euros per win and 190,000 for a draw with additional revenue coming through television markets and money depending on each team's UEFA ranking.
By comparison, the Champions League winners stand to take home around 75 million euros before considerable sums are tacked based on the market pool and coefficient ranking.
The final will be held in the Polish city of Gdansk on May 27, 2020.
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