The German giants raced into a 4-0 lead within the first 35 minutes courtesy of strikes from Sadio Mane, Thomas Muller and a brace from Leon Goretzka, before the hosts pulled two goals back in the second half through Adam Vlkanova and Jan Kliment.
However, Julian Nagelsmann's side came away from Czechia with maximum points and have qualified for the knockout stages for the 19th successive season.
Bayern, who sit top of Group C and five points clear of Inter Milan in second, have also extended their impressive unbeaten run in the Champions League group stage to 32 matches, the longest such run in the competition's history.
Similarly to their comfortable 5-0 victory over Plzen in the reverse fixture last week, Bayern came out the blocks quickly against their Czech counterparts and opened the scoring in the 10th minute when Mane played a neat one-two with Goretzka before dinking the ball over goalkeeper Jindrich Stanek.
Muller then added a second just four minutes later with a simple tap-in inside the six-yard box, before Goretzka netted Bayern's third in the 25th minute with a curling effort into the bottom corner.
With Bayern in cruise control, Mane played Goretzka through on goal before the German midfielder chipped the ball over Stanek to score his second of the night and help the visitors take a four-goal lead into half time.
Bayern appeared to take their foot off the gas slightly and that benefitted Plzen, who pulled one back in the 61st minute when the ball dropped onto the edge of the area for Vlkanovato to strike a sweet volley into the bottom-left corner.
The hosts were then given a glimmer of hope with 15 minutes remaining when Kliment received the ball and swiveled inside the area before firing a clean strike beyond Bayern stopper Sven Ulreich.
However, the Bundesliga champions saw out the closing stages and have now booked their place into the last 16 with two group games remaining.
There is still work to be done for Nagelsmann's side, however, as a victory against Barcelona in their penultimate Group C fixture in two weeks' time will see them qualify as group winners.
Elsewhere in Group C, Barcelona and Inter Milan played out an enthralling 3-3 draw at Camp Nou, with the La Liga giants now at risk of failing to qualify for the last 16 after claiming only four points from their four group games.