Manchester United made a laboured start to their Europa League campaign as they were beaten 1-0 by Feyenoord in Rotterdam on Thursday.
Tonny Vilhena scored the decisive goal for the Eredivisie side in the 79th minute as Nicolai Jorgensen's cut-back cross found the 21-year-old midfielder free in the box to slot home.
Jose Mourinho had made eight changes to the side that lost against Manchester City in the Premier League at the weekend, introducing Marcus Rashford and Anthony Martial into the XI, though he replaced them after an hour with Zlatan Ibrahimovic and Memphis Depay with United failing to fire.
Martial came closest to breaking the deadlock for United in the 24th minute when he put a Matteo Darmian cross wide from close range but they failed to test former Liverpool goalkeeper Brad Jones before Vilhena beat David De Gea with a low effort.
In the other game in Group A, Ukrainian debutants Zorya were only denied a landmark first win by Fenerbahce defender Simon Kjaer's goal in the fifth minute of added time for a 1-1 draw.
Inter Milan also found it tough going in their opener as they fell 2-0 to to Hapoel Be'er Sheva at the San Siro in Group K.
Miguel Vitor's 54th minute strike and a 69th-minute free kick from Maor Bar Buzaglo means that Frank De Boer has now won just one of his opening four fixtures in charge of the Nerazzurri.
Inter's defeat means Southampton top the group after two first-half goals from Charlie Austin and a Jay Rodriguez strike in added time provided a 3-0 win against Sparta Prague, earning Claude Puel a first victory as manager of the club.
Austin put Saints ahead from the penalty spot after five minutes when Costa Nhamoinesu handled in the penalty area, and he added a second on 27 minutes with a header from Cuco Martino's cross, before Rodriguez, on as a substitute for Austin, added a third in the final exchanges of the game.
Roma were held to a 1-1 draw at Viktoria Plzen in Group E.
The visitors took the lead after just four minutes when Ales Mateju fouled Stephan El Shaarawy in the box and Diego Perotti converted the penalty, but Marek Bakos equalised for the Czech side seven minutes later.
Also in Group E, Austria Vienna earned a win 3-2 at Astra Giurgiu thanks to an early Raphael Holzhauser penalty, Kevin Friesenbichler's goal and Alexander Grunwald's free kick.
The visitors held on with 10 men after Cristian Sapunaru scored for Astra and Lukas Rotpuller was sent off.
Serie A side Sassuolo were in control at home to defeat Athletic Bilbao 3-0.
Pol Lirola impressively opened the scoring on the hour mark after a long run into the box, before Gregoire Defrel added a second following Mikel San Jose's defensive miscue, and Matteo Politano added a third.
Rapid Vienna rallied from a goal down to defeat Genk 3-2.
The Belgian side led at half-time thanks to Jamaican teenager Leon Bailey's superb effort from long range, but the hosts recovered quickly after the break with goals from Stefan Schwab and Joelinton, as well as Omar Colley's own goal, and a second from Bailey late on was not enough to draw level.
Giuseppe Rossi's 30-yard strike helped Celta Vigo manage a 1-1 draw at Standard Liege in Group G.
Mathieu Dossevi had given the Belgian side the lead after four minutes before Rossi's dipping shot found the net nine minutes later, and neither side could find a winner.
Ajax came away with a 2-1 win at Panathinaikos in a Group G clash in which the Greek side finished with nine men and the visitors 10.
Marcus Berg put Panathinaikos ahead after just six minutes, but Bertrand Traore equalised 10 minutes before half-time.
Jairo Riedewald put in the rebound after Davy Klaassen's penalty was saved for the winning goal, before first Panathinaikos' Ivan Ivanov and then Ajax's Hakim Ziyech were dismissed, and Wakaso Mubarak saw red in stoppage-time.
Baba Rahman scored his first goal for Schalke to provide a 1-0 win at Nice in Group I.
The Chelsea loanee played a one-two with Max Meyer on the edge of the box before lashing a hard shot in at the near post on 75 minutes.
Joaozinho's first-half goal gave Krasnodar a 1-0 win at Salzburg, the attacker taking advantage after a throw-in somehow eluded three defenders, and the visitors held on after Sergei Petrov's 71st-minute red card.
In Group L, Alexandre Pato and Jonathan Dos Santos scored as Villarreal fought back to win 2-1 against FC Zurich, who had taken a second-minute lead through Armando Sadiku.
The other game in that group saw Osmanlispor run out 2-0 winners against 10-man Steaua Bucharest, thanks to second-half goals from Cheick Diabate and Aminu Umar after Gabriel Enache's sending off.
In Group C, Niko Bungert headed in following a corner to give Mainz a lead over St Etienne, but the French side hit back to draw 1-1 with Robert Beric's equaliser on 88 minutes.
Meanwhile, Anderlecht handled Qabala with a 3-1 victory at home with goals from Lukasz Teodorczyk and Diego Capel either side of Rafael Santos's own goal.
In Group D, Zenit St. Petersburg came all the way back from three down to earn a dramatic 4-3 win at Maccabi Tel Aviv, who saw Eliazer Dasa sent off with two yellow cards in a three-minute span in the second half.
A Haris Medunjanin brace and Vidar Kjartansson goal had the Israeli side 3-0 up after 70 minutes, but Aleksandr Kokorin got a goal back before Dasa's dismissal, and goals from Robert Mak and Giuliano in quick succession brought Zenit level before Luka Djordjevic scored the winner in stoppage time.
AZ Alkmaar could not take advantage of having an extra man against Dundalk in a 1-1 draw.
Stijn Wuytens had put AZ ahead on the hour mark before Stephen O'Donnell earned a second booking for the Irish side, but Ciaran Kilduff's still equalised with a header two minutes from time.
Esteban Cambiasso's sliding finish shortly before half-time was enough to give Olympiakos a 1-0 win at Swiss club Young Boys in Group B.
APOEL rallied to win 2-1 win at home against Astana, Vinicius's 74th-minute goal cancelling out Nemanja Maksimovic's opener before Igor de Camargo's 87th-minute winner.
At 10.69 seconds, Jan Sykora scored the fastest goal in Europa League history for Slovan Liberec, but his side settled for a 2-2 draw at Qarabag in Group J.
Milan Baros carried the ball forward and laid it off at the top of the box for Sykora, who bettered the 13.21 seconds in which Sevilla's Vitolo scored in 2015.
The Azerbaijan side equalised through Michel six minutes later, and after Baros' second-half strike, the hosts again levelled with Rasad Sadiqov's volley deep into stoppage time.
Fiorentina made a slow start to Group J after being held 0-0 by PAOK Salonika in Greece.
Facundo Ferreyra headed home the only goal for Shakhtar Donetsk in their 1-0 win at Konyaspor in Group H, while Braga and Gent played out a 1-1 draw -- Andre Pinto's 24th-minute goal cancelling out Danijel Milicevic's opener.