Tottenham must travel to Anzhi Makhachkala, while Swansea have been paired with Kuban Krasnodar and Wigan with Rubin Kazan.
Andre Villas-Boas's side face another lengthy journey across Europe to Sheriff Tiraspol of Moldova and must also head north to the Arctic Circle outpost of Tromso in Norway.
Michael Laudrup will return to Spain after the Swans were paired with La Liga giants Valencia, as well as St Gallen of Switzerland, while Wigan must squeeze in trips to Maribor of Slovenia and Zulte Waregem of Belgium amid their gruelling Championship schedule.
Tottenham - quarter-finalists last season - reached the group stage thanks to an 8-0 aggregate win over Dinamo Tbilisi, while Swansea secured a 6-3 two-legged win over Petrolul of Romania. Wigan qualified automatically as FA Cup winners.
The top two in each of the 12 groups will go into a knockout round of 32 clubs, including the eight sides that finish third in the Champions League groups.
The first group stage matches will take place on 19 September.
Wigan chief executive Jonathan Jackson was in quietly confident mood after the draw was made.
"Playing in Europe is about experiencing new places and going to new clubs and it's something we are really looking forward to," he said.
"It's a group where we can certainly compete and we won't take anyone likely but we have every chance."
Swansea general manager Alun Cowie also admitted he was excited by what lies ahead for his club.
"From a football point of view Valencia is the team that stood out and for our Spanish contingent they are going to be two great games," he said.
"We have Pablo Hernandez, formerly of Valencia, and six other boys who have played at the very highest level of La Liga and we are going to need that experience.
"All three of us from the UK have Russian opponents and hopefully the fixtures will be kind to us for the Premier League matches afterwards."
GROUP A: Valencia, SWANSEA CITY, Kuban Krasnodar, St Gallen.
GROUP B: PSV Eindhoven, Dinamo Zagreb, Chernomorets Odesa, Ludogorets Razgrad.
GROUP C: Standard Liege, Salzburg, Elfsborg, Esbjerg.
GROUP D: Rubin Kazan, WIGAN ATHLETIC, Maribor, Zulte Waregem.
GROUP E: Fiorentina, Dnipro Dnipropetrovsk, Pacos de Ferreira, Pandurii Targu Jiu.
GROUP F: Bordeaux, Apoel FC, Eintracht Frankfurt, Maccabi Tel-Aviv.
GROUP G: Dynamo Kiev, Genk, Rapid Vienna, FC Thun.
GROUP H: Sevilla, Freiburg, Estoril Praia, Slovan Liberec.
GROUP I: Lyon, Real Betis, Vitoria, Rijeka.
GROUP J: Lazio, Trabzonspor, Legia Warsaw, Apollon Limassol.
GROUP K: TOTTENHAM, Anzhi Makhachkala, FC Sheriff, Tromso.
GROUP L: AZ Alkmaar, PAOK, Maccabi Haifa, Shakhter Karagandy.