Champions League holders Real Madrid slumped to a rare defeat in the competition as they went down 1-0 away to CSKA Moscow on Tuesday, while Jose Mourinho's Manchester United misfired again in a 0-0 draw with Valencia.
While Bayern Munich were also held by Ajax, it was a happier evening for Pep Guardiola's Manchester City as they beat Hoffenheim 2-1, and Juventus were also comfortable winners thanks to Paulo Dybala's hat-trick.
Real were not expected to struggle in Group G as they look to continue their recent dominance of the Champions League, but Julen Lopetegui's side went behind inside two minutes in Moscow following a mistake by Toni Kroos.
The German's drilled backpass turned into a gift for Nikola Vlasic, and the winger on loan from Everton fired past Keylor Navas to put CSKA ahead.
Casemiro hit the post in the first half – one of three attempts that found the woodwork for the visitors – but Real were weakened by the absences of Gareth Bale and Sergio Ramos, while Luka Modric started on the bench.
Rodriguez (L) and Matthijs de Ligt compete for the ball during their Group E clash between Bayern Muenchen and Ajax at Allianz Arena, October 2, 2018. /VCG Photo
CSKA held on, despite having goalkeeper Igor Akinfeev sent off in injury time, and they move above Real to the top of Group G.
"I am sure we will soon be scoring again and winning again," said Lopetegui, whose team have not found the net in three matches.
It was only Madrid's third defeat in the Champions League group stage this decade, but Real will nevertheless expect to bounce back next against Czech champions Viktoria Plzen, who were crushed 5-0 by Roma.
Edin Dzeko scored a hat-trick for the Italian side, with Cengiz Under and Justin Kluivert also netting.
At Old Trafford, the pressure continued to build on Mourinho as Manchester United produced another insipid attacking display in their goalless stalemate with Valencia.
They are now four games without a win, and Mourinho's decision to recall Alexis Sanchez – after dropping the Chilean for the weekend defeat at West Ham United – failed to pay off.
"Our attacking players aren't in their best moments of confidence and individual level," moaned Mourinho. "We thought with three or four chances we would score and win the game."
Colombian midfielder Juan Cuadrado (R) celebrates with Paulo Dybala during their Group H clash between Juventus and Young Boys, October 2, 2018. /VCG Photo
Dybala shines in Ronaldo's absence
Mourinho's side are second in Group H, two points behind Juventus.
Juve eased to victory against 10-man Young Boys in Turin, with Dybala scoring a hat-trick to take centre stage in the absence of Cristiano Ronaldo, who was serving a one-game ban.
Guardiola saw Manchester City come from behind to beat Hoffenheim in Germany in Group F.
David Silva scored three minutes from time to get the Premier League champions back on track after they started their campaign with a 2-1 home defeat against Lyon.
Ishak Belfodil had put Hoffenheim ahead after just 44 seconds, but Sergio Aguero equalized in the eighth minute before Silva's late winner.
Manchester City players celebrate in a huddle after their team beat Group F opponent Hoffenheim, October 2, 2018. /VCG Photo
Manchester City next face Shakhtar Donetsk, who squandered a two-goal lead to draw 2-2 with Lyon in France, in a game played behind closed doors.
Brazilian forward Junior Moraes scored twice for Shakhtar, but Lyon fought back to draw with goals from Moussa Dembele and Leo Dubois.
It was a good result for Lyon, whose fans were missing as a punishment for trouble at a game against CSKA last season, and they now top the group.
Meanwhile, Bayern could not hang on to the early lead given to them against Ajax when Mats Hummels headed in Arjen Robben's cross. Young full-back Noussair Mazraoui equalized to give the Dutch side a 1-1 draw.
Those sides are level atop Group E ahead of Benfica, who won 3-2 in a thriller at AEK Athens with Alfa Semedo scoring the deciding goal.