The Czechs finish third in Group D following victory over nine-man CSKA, meaning coach Pavel Vrba, who is set to take over the Czech national team, leaves the club on a high
Bayern Munich and Manchester City had already earned their spots in the knockout stages of Europe's premier club competition, with the Europa League place the only issue to be decided in the final round of Group D matches.
Pavel Vrba, who was taking charge of his final Plzen match before assuming control of Czech Republic's national team, saw his side come from behind in dramatic fashion after Ahmed Musa's 65th-minute header put CSKA in front.
CSKA's Alan Dzagoev was dismissed for a clash with Vaclav Prochazka, and Plzen soon levelled through Daniel Kolar before Tomas Wagner scored a winner in the final minute of normal time.
There was also time for Pontus Wernbloom to be shown a red card as Plzen extended their European campaign into the new year for a third consecutive season.
Plzen made one change from their 4-2 defeat against Manchester City, with David Limbersky replacing Roman Hubnik in defence.
Dzagoev made his first start since September for CSKA after recovering from a hamstring problem, although Leonid Slutsky was without three key players due to injury.
Defenders Mario Fernandes and Alexei Berezutski were both ruled out, as was striker Seydou Doumbia who had scored twice in the competition so far.
Zoran Tosic of CSKA and Plzen’s Pavel Horvath had early opportunities, but each fired over the crossbar.
Stanislav Tecl was next to threaten after 27 minutes, as he forced visiting goalkeeper Igor Akinfeev into a smart save from the edge of the area.
Musa then wasted the best chance of the half for CSKA after 31 minutes, producing a tame effort when through on goal that was easily saved by Matus Kozacik with his feet.
CSKA brought Milan-bound Honda into the action seven minutes into the second half and, a minute before the hour mark, Dzagoev's long-range strike was too hot for Kozacik to handle, forcing a clearance from Prochazka.
Tecl headed over from a whipped Horvath delivery four minutes later, before Musa showed the Czech how it was done.
The lively striker peeled away at the far post before heading Honda's cross into the ground, but Dzagoev's dismissal for an off-the-ball incident with Prochazka made life uncomfortable for the visitors as Plzen pressed forward.
They were eventually rewarded when Kolar headed home unmarked from Horvath's cross with 14 minutes remaining.
Wagner then converted Frantisek Rajtoral's delivery in the dying stages of the game to ensure Vrba's reign ended on a notable high.