The Spain playmaker has only recently returned from yet another leg muscle injury but looked close to his dazzling best in scoring the holders' 10th-minute opener before being replaced by Seydou Keita late on.
Iniesta combined superbly with Lionel Messi for the goal, the Argentine World Player of the Year providing the assist after Iniesta had set him up to score against Racing Santander in La Liga on Saturday.
A subsequent passage of play in which Iniesta bamboozled the Plzen defence with his quick feet and razor-sharp skills had the 70,000 Nou Camp fans in the giant arena chanting his name.
"You already know that when he is on song he is unique and he has returned from the injury in great shape," Barca coach Pep Guardiola told a news conference.
"He works hard, he scores more goals than you would think and the way he can throw the opposition off balance is so important for us," the former Spain and Barca midfielder added.
"Last year he was vital and now we just hope he can be important again. We will try to look after him and make sure he is fine."
Barca's victory, which extended their unbeaten run to 19 in all competitions, lifted them to seven points after three of six Group H games, level with Italian side AC Milan who beat BATE Borisov of Belarus 2-0.
Plzen and BATE, who lost 5-0 at home to Barca on matchday two, each have one point.
While Iniesta dazzled, it was a frustrating night for Messi, the competition's top scorer the past three seasons.
The 24-year-old twice struck the post and was several times denied by last-ditch tackles following trademark weaving runs.
Guardiola dismissed questions about Barca's profligacy in front of goal on Wednesday, when they had 18 attempts but only managed to get four of them on target.
Plzen's failure to muster a shot was only the second time that has happened in a Champions League game in the last five seasons after English Premier League side Arsenal suffered the same fate against Barca last season.
"Scoring goals is the most difficult part of soccer," Guardiola said.
"When Messi doesn't score that becomes news. Imagine the level he has reached if that is the case."
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