Four of Los Blancos' goals came in a 19-minute spell in the first half, having struggled up until that point, and Toni Kroos added a fifth after the restart.
Two weeks on from stuttering to a 2-1 win against the same opponents, the reigning European champions made light work of this fourth Group G outing, earning a comfortable win that takes them above Roma at the top.
Plzen are now unable to finish in the top two spots, leaving just CSKA Moscow - five points worse off - in pursuit of Madrid and Roma with two games to go.
Things could have turned out much differently on the night as Real initially struggled in an unorthodox 4-3-3 formation that had Dani Ceballos - in for Luka Modric in one of two changes - fielded just behind Karim Benzema.
Viktoria could not capitalise on the uncertainty in the Madrid ranks, though, coming closest to a breakthrough when Patrik Hrosovsky - on the scoresheet in the 2-1 loss at the Bernabeu a fortnight ago - sent in a powerful cross that hit Nacho Fernandez and came back off the crossbar.
With a quarter of the match played the visitors finally started to show just why they have made it through to at least the semi-finals seven years running, getting off the mark through a fine Benzema strike.
The French striker took the ball past one player and then dragged it past another before slotting it through the legs of Ales Hruska for his 200th goal in the famous white strip.
Casemiro guided a simple second into the corner of the net after being left totally unmarked from a corner, before Benzema helped himself to another in almost identical circumstances, this time once picked out by Gareth Bale's headed pass four yards out.
Bale, denied earlier in the half through a Hruska save, joined Benzema and Casemiro on the scoresheet before the interval with a powerful finish at the back post following some good play from Ceballos down the left.
Viktoria, who are now winless in 10 Champions League matches, attempted to make a good fist of it as Jan Kopic and Hrosovsky both got away shots in the opening 10 minutes of the second half that Thibaut Courtois - preferred to Keylor Navas here - had to deal with.
With an eye on Sunday's trip to Celta Vigo, the second of four successive away matches, Solari introduced youngster Javi Sanchez for a European debut.
It was a player with far more experience on the continental stage who added Real's fifth, with Kroos curling the ball into the top corner after being teed up by substitute forward Vinicius Junior.
Tomas Chory was denied a late consolation by a Courtois save, shortly before Bale sent a first-time shot against the bar, ensuring that Solari's men had a clean sheet to go with their third successive win under the stand-in boss.
VIKTORIA PLZEN (4-2-3-1): Hruska; Limbersky, Hubnik, Hejda, Reznik; Prochazka, Hrosovsky; Kopic, Cermak (Horava 61'), Havel (Petrzela 38'); Chory (Reznicek 80')
REAL MADRID (4-3-3): Courtois; Odriozola, Ramos (Sanchez 59'), Nacho, Reguilon; Kroos (Isco 73'), Casemiro, Ceballos; Vazquez, Benzema (Vinicius 62'), Bale