Champions League holders Real Madrid slumped to a rare defeat in the competition as they went down 1-0 away to CSKA Moscow, 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.
CSKA held on, despite having goalkeeper Igor Akinfeev sent off in injury time, and they move above Real to the top of Group G.
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 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.
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.
"We were without Cristiano, and at times it is easier with him in the side, but we have to be a great team both with and without him," said Dybala.
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 equalised in the eighth minute before Silva's late winner.
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.
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 equalised 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.
Results: Group E: AEK Athens: 2 lt to Benfica: 3; Bayern Munich: 1 drew with Ajax: 1.
Group F: Hoffenheim: 1 lt to Manchester City: 2; Lyon: 2 drew with Shakhtar Donetsk: 2.
Group G: Roma: 5 bt Viktoria Plzen: 0; CSKA Moscow: 1 bt Real Madrid: 0.
Group H: Juventus: 3 bt Young Boys: 0; Manchester United: 0 drew with Valencia: 0.