Reigning Czech champions Viktoria are without a point at the midway stage in Group C and found themselves three goals down after 21 minutes at the Allianz Arena.
Serge Gnabry and Sadio Mane netted after Sane had opened the scoring in Tuesday's contest as Bayern cruised towards a third win out of three in this season's competition.
Sane's second was swiftly followed by a strike from substitute Eric Choupo-Moting, with Bayern settling for five goals ahead of their big Bundesliga clash with Borussia Dortmund.
Bayern were without Thomas Muller and Joshua Kimmich, who tested positive for COVID-19, but were ahead inside seven minutes thanks to Sane's powerful shot from 18 yards.
Gnabry, fielded through the centre of Bayern's attack, slotted home a second six minutes later with a clinical finish after being played in by Leon Goretzka at the end of a counter.
Some poor Plzen defending allowed Mane to waltz through and score a third for Bayern, who had a Jamal Musiala goal ruled out before half-time due to an offside infringement.
Sane doubled his tally after controlling Mane's pass with a sublime first touch and firing past Marian Tvrdon, with that proving to be his final meaningful act before being replaced.
It was left to Choupo-Moting to round off the scoring prior to the hour mark with a shot that went in off the post following another precise pass from Goretzka.