Victor Osimhen scored twice as Galatasaray inflicted a first Europa League defeat of the season on Tottenham with a 3-2 victory in Istanbul on Thursday, while Manchester United got their first win on the board by beating PAOK Thessaloniki.
The Turkish champions have 10 points from four games and have all but secured qualification for at least the knock-out play-off round, while Spurs sit in seventh place after losing their 100 per cent record in Europe's second-tier club competition.
"We expected it to be a difficult match. We encountered a team as we expected. They have dangerous players," said Tottenham manager Ange Postecoglou.
"We lost because we could not show what we wanted in the first half. Both teams are doing well in Europe."
Galatasaray took an early lead when Yunus Akgun smashed a sensational long-range volley into the top corner in the sixth minute.
But the visitors hit back just 12 minutes later as teenage striker Will Lankshear marked just his second first-team appearance with a goal by tapping in Brennan Johnson's pass across the six-yard box.
Galatasaray took control before half time, though, as Osimhen scored twice in the space of eight minutes.
The Nigerian star, who is on a season-long loan from Napoli, fired them back in front just after the half-hour mark, before cleverly volleying Dries Mertens' cross past Tottenham goalkeeper Fraser Forster. It was his sixth goal in eight appearances for the Turkish club.
Any hope of a Tottenham comeback were extinguished when Lankshear was sent off for two yellow-card offences in quick succession in the second half.
Dominic Solanke pulled one back in the 69th minute, shortly after being brought on by Postecoglou, but Galatasaray held on with relative comfort.
United finally win in Europe
Amad Diallo scored twice as Manchester United beat PAOK 2-0 at Old Trafford in their first Europa League game since sacking Erik ten Hag.
The Ivorian winger put United ahead early in the second half with a header across goal that bounced in at the far post.
Diallo secured the hosts a much-needed three points, after three previous draws, with 13 minutes remaining with a wonderful individual effort.
"He has been incredible in training, he always trains well and is asking me to do more," interim manager Ruud van Nistelrooy said of Diallo.
Van Nistelrooy's next and final game in charge will be the Premier League visit of Leicester this weekend, before Ruben Amorim takes over after the international break.
"Sunday is another one and I'm so focused on doing that so I'm not thinking of what is next."
Lazio are the only team with four wins from four games after Pedro scored an injury-time winner in a 2-1 success against Porto.
Alessio Romagnoli gave the Romans the lead on the stroke of half time, before Stephen Eustaquio levelled for Porto.
Ajax sit in second place, two points behind Lazio, after romping to a 5-0 thrashing of Maccabi Tel Aviv.
Omar Marmoush's 13th goal of the season clinched Eintracht Frankfurt, who are fourth behind Galatasaray on goals scored, a 1-0 win against Slavia Prague.
The Egyptian clipped a superb free-kick in off the crossbar shortly after the break.
Athletic Bilbao came from behind to grab a 2-1 success at Ludogorets.
Inaki Williams and Nico Serrano both scored in a two-minute burst from the Basque club.
Roma's disappointing form this season continued as Kevin Mac Allister's goal 13 minutes from time secured Union Saint-Gilloise their second point of the competition with a 1-1 draw in Belgium.
Elsewhere, Rangers held Olympiakos to a 1-1 draw in Greece, while Hoffenheim and Lyon both scored deep into added time in a dramatic 2-2 draw.
