City were frustrated by the Czech champions in the first half at the compact Doosan Arena but burst into life after the break with goals from Edin Dzeko, Yaya Toure and Sergio Aguero. The lively Aguero had also hit the post in the first half while Matus Kozacik also made good early saves from Dzeko and Jesus Navas in the Group D encounter.
The result was the perfect start in the competition for Manuel Pellegrini, City's new coach, and lifted spirits after a mixed start to the campaign ahead of Sunday's derby against Manchester United.
Pellegrini's record in the Champions League, having taken Villarreal to the semi-finals and Malaga to the last eight, was one of City's prime reasons for appointing him in the summer. A day after his 60th birthday, he got what he hopes will be another prolonged run up and running with an ultimately convincing win. Champions Bayern Munich will doubtless provide a sterner test in their next fixture but City's challenge is already looking better than last season's, when they failed to win a match.
It took City time to make their mark against a Plzen side unbeaten in 14 games this season but once the deadlock was broken the result was never in doubt. "In the first half we had chances, but in the second half we played really well," Pellegrini said. "We played with movement, we were able to create space because with 10 players behind the ball, it's hard to score.
"We know the Champions League is very difficult and there are no easy games. Winning away is important. Those three points might be very important in getting to next round."