The Russians, who lost 3-0 at Bayern Munich in their opening fixture, trailed to Frantisek Rajtoral's fourth-minute strike at the Stadion Petrovskiy in St Petersburg with torrential rain in Moscow having forced them to move the fixture.
But Zoran Tosic's deflected 19th-minute effort, which ended a 398-minute wait for a goal for Leonid Slutski's men in all competitions, paved the way for Honda to fire them ahead 10 minutes later with an exquisitely-placed shot.
Radim Reznik's unfortunate late own goal, for which an horrendous error by keeper Matus Kozacik was to blame, sealed the win, although opposite number Igor Akinfeev had a moment to forget in injury-time when he made a mess of punching clear a cross and Marek Bakos reduced the deficit.
It took the Czechs, who lost 3-0 at home to Manchester City last month, less than four minutes to force their way in front, although the opening goal arrived courtesy of a slice of good fortune.
Milan Petrzela's shot cannoned off defender Sergei Ignashevich and dropped into the path of supporting full-back Rajtoral, whose right-foot finish from a tight angle beat Akinfeev at his near post.
Plzen could have been out of sight with the game just 16 minutes old after Daniel Kolar headed just wide with Akinfeev having misjudged a left-wing cross, and the keeper did well to block Bakos' shot when he was played in by Petrzela.
But they were made to pay for not making the most of their early dominance when Ahmed Musa left Roman Hubnik for dead as he ran on to Steven Zuber's pass and squared for Tosic, whose shot was deflected past Kozacik by defender Vaclav Prochazka.
Worse was to follow for the visitors when Zuber and Tosic broke at pace to slide in Honda, who deftly clipped the ball past Kosacik with the outside of his left foot to make it 2-1 with 29 minutes gone.
Musa should have made it 3-1 within four minutes of the restart, but turned Kirill Nababkin's cross against the post from point-blank range, but Honda had to hack Kolar's 53rd-minute shot off the line at the other end.
Petrzela curled a left-footed effort just wide six minutes later with Plzen responding, but their hopes were dashed 12 minutes from time when Kozacik allowed Reznik's back-pass to roll under his boot and into the empty net, although Akinfeev was left equally red-faced at the death as he allowed Bakos to head home unopposed.