Arsenal face punishing away trips in their Europa League campaign after Friday's group stage draw pitted them against BATE Borisov and Red Star Belgrade, while Everton face a tough group including last season's semi-finalist Olympique Lyonnais.
Arsene Wenger's side, who failed to reach the Champions League for the first time since 1997, face a 4,500km round trip to face Belarusian champion BATE and can expect an intimidating atmosphere in their trip to Serbia to face Red Star.
They will also meet Bundesliga side FC Cologne in Group H.
Everton, the other Premier League side in the Europa League and who return to the competition after a three-year absence, take on Serie A side Atalanta in Group E, who are back in European football for the first time in 26 years.
Ronald Koeman's men will also face Cypriot side Apollon Limassol and Lyon, who were knocked out of the final four last season by eventual runners up Ajax Amsterdam.
AC Milan are the favourite to win the tournament after spending more than 200m euros ($236.10m) on new signings this season including Lucas Biglia, Andre Silva and Leonardo Bonucci.
They will face Austria Vienna, HNK Rijeka and AEK Athens in Group D.
Villarreal, Maccabi Tel-Aviv, Astana, Slavia Prague.
Dynamo Kiev, Young Boys, Partizan Belgrade, Skenderbeu.
Braga, Ludogorets, Hoffenheim, Istanbul Basaksehir.
Milan, Austria Vienna, Rijeka, AEK Athens.
Lyon, Everton, Atalanta, Apollon.
Copenhagen, Lokomotiv Moscow, Sheriff Tiraspol, Zlin.
Viktoria Plzen, FCSB, Hapoel Beer-Sheva, Lugano.
Arsenal, BATE Borisov, Cologne, Crvena Zvezda.
Salzburg, Marseille, Vitoria SC, Konyaspor.
Athletic Bilbao, Hertha Berlin, Zorya Luhansk, Ostersund.
Lazio, Nice, Zulte Waregem, Vitesse.
Zenit St Petersburg, Real Sociedad, Rosenborg, Vardar Skopje.