Borussia Dortmund began their Europa League campaign with a 1-0 win away to Wolfsberger AC on Thursday.
Jonas Hofmann scored the only goal in the 14th minute to help Dortmund leave Austria with a slim advantage in the third qualifying round.
Pierre-Emerick Aubameyang sent Henrikh Mkhitaryan through on goal and the Armenian unselfishly passed on to Hofmann to slot into an empty net.
West Ham squandered a two-goal lead after James Collins was sent off as they once again toiled with 10 men in a 2-2 draw at home to FC Astra.
Enner Valencia and Mauro Zarate had put the Hammers well in control against Astra Giurgiu before Collins became the third player to be sent off in five games under Slaven Bilic, who was also dismissed by referee Adrien Jaccottet in the closing stages.
Despite dominating before the red card, West Ham could not deal with their Romanian opponents who made the most of their numerical advantage as Fernando Boldrin thrashed home, with debutant Angelo Ogbonna then scoring an own goal.
Southampton enjoyed a dream return to continental football, hitting three past Vitesse Arnhem as they secured a first European win since 1981.
Last year's club-best Premier League finish brought with it qualification for the Europa League, which Ronald Koeman's men started with a 3-0 win thanks to goals from Graziano Pelle, Dusan Tadic and Shane Long.
Pelle opened the scoring in the 36th minute after latching onto a Sadio Mane through ball, and Mane then won a penalty that Dusan Tadic converted before the break.
Long scored on the break in the 84th minute to cap the scoring.
Serie A side Sampdoria were embarrassed at home by Vojvodina 4-0.
The Serbian team led by the fourth minute through Mirko Ivanic, then widened their advantage after break with a goal by Aleksandar Stanisavljevic and Ognjen Ozegovic's brace.
Sampdoria only qualified after Genoa failed to secure a European license. President Massimo Ferrero apologised to fans after the match, though coach Walter Zenga said the "real beating" would do the club good.
Crowd trouble caused the abandonment of the match between Kukesi and Legia Warsaw in Albania.
Legia had just taken a 2-1 lead when their player Ondrej Duda was hit by an object thrown from the stand.
Play was immediately suspended as Duda was taken off the field on a stretcher and had his head bandaged.
Javier Eraso scored in each half to help Athletic Bilbao begin their qualifying campaign with a 2-0 win over Azerbaijan's Inter Baku.
Bordeaux cruised to a 3-0 win against AEK Larnaca of Cyprus.
The game was goalless at half-time before Andre Biyogo Poko, Cheick Diabate and Nicolas Maurice-Belay scored after the break.
St Etienne came away from their trip to Romania with a 3-0 win over Tirgu Mures.
Ismael Diomande found the net in the 24 minute before a second-half brace by Romain Hamouma gave the French side a considerable advantage for the second leg.
Standard Liege managed a 2-1 win at home against Zeljeznicar.
An Aleksandar Kosoric put the hosts ahead early and Anthony Knockaert doubled their advantage, but Ognjen Djelmic's away goal will give the Bosnia side hope.
AZ Alkmaar defeated Istanbul Basaksehir 2-0, a task made easier after goalkeeper Volkan Babacan's 14th-minute red card.
Jop van der Linden scored the resulting penalty and Vincent Janssen added a second goal after the break.
U.S. international striker Aron Johannsson played the second half after returning from international duty at the Gold Cup.
Kenny McLean scored a crucial away goal but Aberdeen lost 2-1 to Kairat Almaty in Kazakhstan.
The Dons found themselves two down inside the first quarter after Mikhail Bakaev and Bauyrzhan Islamkhan scored, but McLean came off the bench to give them hope for the second leg.