The visitors provided a late scare thanks to Marek Bakos's 91st minute goal but the home side held on to take the points
Plzen created a number of chances as they looked to claim the spoils in the first competitive meeting between the two sides, but it was CSKA who secured all three points.
Tosic and Honda both netted and an own goal from Reznik allowed CSKA to establish a 3-1 lead before Bakos pulled one back late on.
Ahmed Musa also struck the post as CSKA produced a vibrant display to suggest that they have an outside chance of progressing from a group that contains Manchester City and Bayern Munich.
CSKA - missing the likes of Alan Dzagoev and Seydou Doumbia through injury - made two changes to the side defeated 2-0 by Terek Grozny in domestic competition last Saturday, Georgi Schennikov replacing Vasili Berezutski in defence, while Rasmus Elm took the place of Georgi Milanov in the midfield.
Visiting coach Pavel Vrba also elected to rotate his squad, with Jan Kovarik, Daniel Kolar and Bakos all coming into the side.
Plzen took the lead with the first real chance of the game after four minutes, Rajtoral slotting home at the far post after Milan Petrzela's effort had been deflected into his path by Sergei Ignashevich.
The Czech side came close to doubling their advantage on 14 minutes when attacking midfielder Kolar headed wide after CSKA goalkeeper Igor Akinfeev had made the ill-advised decision to come out and try and claim a high ball into the box.
Some heroic defending from Pontus Wernbloom denied Vrba's men the chance to extend their advantage. The CSKA midfielder cleared Bakos' shot off the line at the end of a superb counter-attack from Plzen.
CSKA appeared to gain confidence following that let-off and duly equalised as Tosic's deflected strike squirmed past Matus Kozacik after the winger had collected Musa's square pass.
The hosts began to dictate play following their leveller, with Honda looking dangerous as the Russian side began to pick apart the Plzen defence.
And it was Honda who put CSKA ahead just before the half-hour mark, the Japan international lofting a composed finish over Kozacik after being played through by Tosic.
Both sides traded chances in the closing stages of the first half as Steven Zuber twice went close for CSKA before Rajtoral tested Akinfeev in injury-time.
CSKA almost killed the game off four minutes into the second half when Musa struck the woodwork after latching on to Kirill Nababkin's near-post cross.
Plzen remained a dangerous attacking threat, though, and they were denied by a goal-line clearance for the second time as Honda showed great awareness to prevent Kolar from finding the net.
The visitors were made to pay for their profligacy 12 minutes from time as defender Reznik's attempted backpass went under Kozacik's foot and into the net.
Bakos pulled one back with a close-range header, but it came too late for Plzen to mount a comeback.