
The Blues' win was one of six for visiting sides on a night on which Celtic were the only home side to win.
The Scottish champions beat the reigning champions AC Milan 2-1 through Australian Scott McDonald's injury time goal. The other game in Group D saw Shakhtar Donetsk win 1-0 at Benfica.
In Valencia new Chelsea coach Avram Grant, who took over after Jose Mourinho was sacked following Chelsea's disappointing 1-1 draw against Rosenborg in their opening Champions League game, started with the same side that played against the Norwegian club.
The Israeli had the worst possible starts to his Champions League career as David Villa opened the scoring for Valencia after just nine minutes benefiting from a Micheal Essien deflection.
To their credit, the Premiership club were not disheartened by the goal and continued going forward. They were rewarded in the 21st minute as Joe Cole turned a crisp Didier Drogba cross into the net.
They scored the winner in the 70th minute after a brilliant defence-splitting pass from Cole found Drogba and the Ivorian international went into the area before scoring.
Captain John Terry, who played with a face mask after suffering a fracture on the weekend, said that the victory was built on many great performances.
"We needed that. It shows that regardless at who is in charge we have a great team spirit. Maybe something was missing in the games before.
"In the match we were fighting for each other. We needed a great performance as it has been a difficult period, but hopefully this can kickstart a great run," he said.
Grant said that he had told his players before the match that they went to Valencia to win. "We did what we wanted to do and we did it in the right way.
"We dominated in the second half and you saw the attitude in the last two weeks. Everybody worked for each other. It was also good to finish the game with 11 players, which we have not done in the last few games."
Chelse lead the group on four points from Schalke 04, who won 2-0 at Rosenborg through goals by Jermaine Jones and Kevin Kuranyi. The Bundesliga side has three points, as do Valenica.
In Group A Porto won 1-0 at Besiktas, while last season's losing finalists Liverpool lost 1-0 at home to Marseille, for whom Mathieu Valbuena scored midway through the second half.
Liverpool coach Rafael Benitez said that his side had simply not performed on the night. "It certainly was not a night like many European Cup nights we have had before.
"But you can't blame the fans. The side did not play well at all. We tried changing players, but that did not help either."
Marseille leads the group with six points, while Porto have four. Liverpool are third on one point, while Besiktas have yet to score a point.
Dutch international Ruud Van Nistelrooy scored twice for Real Madrid at Lazio, but Macedonian international Goran Pandev twice equalized for the home side for a share of the spoils in their Group C game.
Greek club Olympiacos came from behind at Werder Bremen to stun the Bundesliga club 3-1 in the other group game. The result sees them top the group on four points on goal difference from Real Madrid. Lazio have two points, while Bremen have none.
In Lisbon Benfica's hopes of reaching the knock-out stage suffered a setback as Ukrainian club Shakhtar Donetsk won 1-0 after Brazilains Fernandinho and Jadson combined to give the latter the opportunity shortly before the break in their Group D game.
In Glasgow Celtic opened the scoring against the reigning champions AC Milan on the hour as Stephen McManus found the back of the net after a corner. Brazilian goalkeeper Dida could do nothing as the ball took a deflection off Yoann Gourcuff.
Milan equalized in the 68th minute through a Kaka penalty awarded after Lee Naylor brought down Massimo Ambrosini in the area.
Australian Scott McDonald gave the home side a historic victory with an injury time goal to keep alive their hopes of advancing. Milan and Celtic are both on three points, while Shakthar have six. Benfica have lost both games.
DPA