Bosnian striker Edin Dzeko scored in the 48th minute with a low shot past helpless Pilsen keeper Matus Kozacik after being set up by Sergio Aguero.
Five minutes later, Yaya Toure sent a superb curling shot from outside the box into the top corner of Kozacik's goal.
Another five minutes passed and Aguero, a constant threat for the injury-plagued Pilsen defence, made it 3-0 with a low left-footed strike. "It's very important to start the Champions League winning away," said City's Chilean manager Manuel Pellegrini, who took charge before this season. "Winning away in the Champions League and scoring three goals, having at least three or four more clear chances to score and having a clean sheet again, that would give a lot of confidence to the players for the next games," he added.
Dzeko said he hoped this result will allow City to find their true form in Europe. "The first half was tricky. We had chances to score then I scored in the second half and after that it was easier for us," he said. "I hope we'll see the real Manchester City because the last two years were disappointing for the fans and the club," he told Sky Sports. "The target is going into the second round but we know it's always difficult."
Big-spending City, sitting fourth in the Premier League with seven points from four games, have never made it to the Champions League knockout phase in their two appearances to date.
But they started this year's mission in style. Jesus Navas produced the first shot on goal in the seventh minute, tipped over the crossbar by a diving Kozacik.
The Slovak keeper also stopped a Dzeko header from close range and then a low shot by Aguero just before half-time.
Aguero beat Kozacik in the 26th minute, but his low shot hit the post and the keeper then stopped a powerful follow-up from Aleksandar Kolarov.
It was the first time Pilsen had played a Champions League game in their home city, famous for its Pilsner beer, after being exiled to Prague for the 2011/2012 edition as their stadium had failed to meet UEFA requirements.
But the team that beat Atletico Madrid and Napoli in last season's Europa League showed very little going forward on Tuesday.
Pilsen's stocky 38-year-old captain Pavel Horvath tested Joe Hart with a free-kick, but the England international managed to keep the effort out, just like another long-range Horvath attempt, both of which came in the first half.
In the second half, Dzeko sent two chances over the bar shortly after opening the score and Aguero had two shots turned away by a diving Kozacik before narrowly missing the target in the last minute.
Pilsen's Tomas Horava then hit the woodwork with a volley just before the end in a rare chance for the home side. "We were lucky in the first half to leave the pitch at 0-0," said Pilsen manager Pavel Vrba. "Our mistake before the first goal influenced the result. The second goal was a beauty and it decided the game."
Giving City a boost ahead of Sunday's Premier League clash with bitter rivals Manchester United, captain Vincent Kompany played the whole game after recovering from a groin injury.
But defenders Martin Demichelis, Micah Richards and Gael Clichy as well as midfielder David Silva remained sidelined. (AFP)
