PSV Eindhoven went down to a shock home defeat in their Europa League Group B opener against Ludogorets.
The Dutch side were expected to get off to a winning start but goals from Roman Bezjak and Virgil Misidjan in the second half gave the visitors all three points.
Two goals in three second-half minutes from Oleksiy Antonov and Franck Djadjedje gave Chornomorets a surprise 2-1 win over Dinamo Zagreb, who had led through Junior Fernandes, in the other Group B clash.
In Group L, Shakhter Karagandy led through George Canas' penalty but were pegged back in the last 15 minutes by PAOK Salonika, for whom Stefanos Athanasiadis and Zvonimir Vukic scored, while Johann Berg Gudmundsson scored the only goal as AZ Alkmaar won 1-0 at Maccabi Haifa.
Substitute Julien Gorius scored the only goal as Genk won at Dynamo Kiev in Group G, while Christian Schneuwly made the breakthrough as FC Thun downed Rapid Vienna.
A second-half resurgence from Liberec saw them leave Freiburg with a 2-2 draw in Group H.
The Bundesliga side were dominant for an hour and eased into a 2-0 lead before half-time but the game changed in the last half-hour as Vladislav Kalitvintsev and Michael Rabusic cancelled out Julian Schuster's penalty and Admir Mehmedi's follow-up.
Kevin Gameiro emerged from the bench to fire Sevilla to a narrow 2-1 victory at Estoril. Vitolo had the Spaniards ahead but Bruno Miguel equalised for the hosts.
Guimaraes cruised to a 4-0 win over Rijeka in Group I, with Abdoulaye Ba, Nii Plange, Moussa Maazou and Felipe Andre Andre on target, while Real Betis and Lyon drew 0-0 in Spain.
Hernanes' second-half goal earned Lazio a deserved 1-0 victory at home to Group J rivals Legia Warsaw, while Trabzonspor came from behind to win 2-1 at Apollon Limassol with goals from Florent Malouda and substitute Yusuf Erdogan, after Gaston Sangoy's penalty had edged the Cypriots ahead.
Swansea recorded the most famous win in their history as their campaign began with a 3-0 dismantling of 10-man Valencia.
The home side were forced to play 80 minutes with 10 men after defender Adil Rami saw red for hauling down Wilfried Bony.
The striker went on to give Swansea the lead in the 14th minute with his fifth goal in eight games, firing home with the help of a deflection.
Michu and a wonderful Jonathan de Guzman free-kick completed the scoring in the second half as the Swans cruised to victory at a stunned Mestalla.
In the other Group A game, St Gallen beat 10-man Kuban Krasnodor 2-0, with Goran Karanovic and Marco Mathys scoring. The visitors' Charles Kabore was dismissed for a second booking in injury time.
Jermain Defoe (2) and Christian Eriksen scored in Tottenham's 3-0 win over Tromso, although the English side were left sweating over injuries to Mousa Dembele, Danny Rose and Younes Kaboul.
FC Sheriff and Anzhi Makhachkala finished goalless in Group K's other match.
Wigan drew 0-0 at Zulte Waregem, while also in Group D, Venezuela international Salomon Rondon turned on the style as Rubin Kazan beat Maribor 5-2 in Slovenia.
Gokdeniz Karadeniz, Ivan Marcano, Roman Eremenko and Alexander Ryazantsev scored but Rondon was the star turn and it was fitting that he put the game to bed with a fourth after Martin Milec had made it 2-1 and Nusmir Fajic 3-2 at different stages. Ryazantsev's strike merely topped things off.
In Group C, Jonathan Soriano scored a hat-trick, including a penalty, as Salzburg secured a comfortable 4-0 opening-night victory over Elfsborg, after Brazilian striker Alan had opened the scoring.
Substitute Mushaga Bakenga scored five minutes into stoppage-time to earn Esbjerg a shock 2-1 Group C victory at Standard Liege.
Eintracht Frankfurt eased to a 3-0 victory against Bordeaux to make it five wins from their last six matches in all competitions, with Vaclav Kadlec, Marco Russ and Constant Djakpa all on target in the opening hour.
The other Group F match finished goalless - with substitute Barach Yitzhaki missing a last-gasp penalty for Maccabi Tel Aviv at home to Apoel Nicosia.
Also winning 3-0 were Fiorentina in Group E as they saw off Pacos Ferreira with goals from Gonzalo Rodriguez, Ryder Matos and Giuseppe Rossi. A first-half goal from Ruslan Rotan was all that separated Dnipro from Romanian hosts Pandurii Targu-Jiu.