Champions League favourites Real Madrid had to come from behind to beat Porto 3-1, holders AC Milan were held 0-0 by Celta Vigo and Manchester United lost 2-1 at VfB Stuttgart on a night of surprises on Wednesday.
Chelsea suffered a shock 2-0 defeat by 10-man Besiktas at Stamford Bridge, while Lazio had to come from two goals down to draw 2-2 with Sparta Prague in Rome.
Red cards were also flourished as Panathinaikos had a player sent off but grabbed a late equaliser to hold Rangers 1-1 in Greece, while Olympique Marseille hammered 10-man Partizan Belgrade 3-0 with a Didier Drogba hat-trick.
The unexpected began after just seven minutes in Portugal, where Costinha put Porto ahead against Real and the hosts went on to dominate possession.
However, they conceded an Ivan Helguera equaliser, fell behind to a Santiago Solari strike and had their fate sealed after the break by a Zinedine Zidane volley.
Real's Portuguese coach Carlos Queiroz said: "It's always hard when you are losing at the start, but we knew the team was well prepared and confident. Porto are difficult, especially in dead-ball situations."
The win kept Real firmly at the top of Group F with six points, followed by the team they trounced 4-2 a fortnight ago, Marseille.
The French club's task at the Stade Velodrome was eased by a red card in first-half stoppage time for Partizan's Andrija Delibasic.
Milan stayed top of Group H with four points following their draw in Spain, while Ajax Amsterdam were 2-0 winners over Club Bruges with a brace from Wesley Sonck.
Milan's frustrated coach Carlo Ancelotti said: "I had hoped for more from my team. We played a poor game and lacked sharpness in attack."
Ajax are second in the group on three points, ahead of Celta on two.
MISERABLE NIGHT
But on a miserable night for English clubs there were humbling defeats for United, who had demolished Panathinaikos 5-0 a fortnight ago, and Chelsea, also looking for a second win.
Stuttgart, top of the Bundesliga without conceding a goal this season, hit Alex Ferguson's side with two second-half goals on the break in the space of two minutes by Imre Szabics and Kevin Kuranyi.
United, Champions League winners in 1999, were back in the game when Dutch striker Ruud van Nistelrooy converted a 67th minute penalty but were lucky to stay in it when U.S. keeper Tim Howard saved a penalty.
Savouring the moment, VfB Stuttgart coach Felix Magath said: "This is one of the nicest victories in my career."
Ferguson had no difficulty identifying the source of his side's problems, saying: "Our defence was poor tonight and that's something we have to work on."
Rangers' draw propelled them a point clear at the top of Group E, ahead of Stuttgart and United, the Scottish champions' next opponents.
Emerson gave Rangers a 35th minute lead but they failed to prevent Pantelis Konstantinidis making it all-square three minutes from the end despite the Greeks having Yiannis Goumas dismissed on 47 minutes.
Chelsea's squad has been assembled at a cost of 111 million pounds ($184.5 million) but their night was effectively over after half an hour as Sergen Yalcin's finishing and some comic-book defending guided Besiktas to victory.
The Turkish champions played the last 40 minutes with 10 men after striker Ilhan Mansiz was red-carded for twice kicking the ball away after the referee had whistled.
"We started well. We tried to score. Then we made two mistakes for the goals," said Chelsea coach Claudio Ranieri.
"When you make mistakes in Champions League it's a goal, 99 percent of the time."
Lazio went a point clear of both Besiktas and Chelsea as Group G leaders on four points after their draw at the Olympic Stadium.
Striker Simone Inzaghi scored twice after the break, the second from the penalty spot, after first-half goals from Libor Sionko and Karel Poborsky had given Sparta the lead.
Lazio coach Roberto Mancini said: "I'm happy with the way my players reacted, especially in the second half. It's not easy to come back from two goals down."