A late Lucas Ocampos goal stunned Leverkusen on Matchday 5 as they fell to a 1-0 loss at home despite dominating on Wednesday night.
With Zenit beating Benfica in the early start, qualification was assured for the Germans before they kicked a ball, but there was no letting up for Schmidt's side who named a full-strength team, eager to secure top spot and a favourable draw in the next round.
They came into the match on the back of an impressive 3-1 victory in Hannover on Saturday, and started superbly with Hakan Calhanoglu testing Daniel Subasić with a long range drives just two minutes in.
The Bundesliga giants were occupying the ball in large spells but were struggling to break through a stern Monaco defence that had conceded just once in four European games this season.
Gonzalo Castro and Wendell struck shots off-target before Calhanoglu and Heung-Min Son also tried their luck, but were struggling to test the Croatian goalkeeper.
It was a frustrating first-half for the German side, but Calhanoglu - usually known for his set-piece quality - was the man most likely to break the deadlock, and went close again when he struck a header straight at the Monaco stopper.
Former Leverkusen striker Dimitar Berbatov had the French side's only shot of the first half when he blazed a long-range strike harmlessly wide of Bernd Leno's goal, and it seemed a matter of when, not if the home side took the lead.
The second period started in much the same vain as the first, with Giuilo Donati firing a tame shot wide, before Calhanolgu went closest when he forced Subasić into a smart save.
Schmidt felt he had to change things to force a result, and Josip Drmić was the man he turned too, making way for Son after an hour. The Swiss international nearly made the perfect start when he latched onto a slick pass, but snatched his shot off target.
Leonardo Jardim then made his first change when he brought on Lucas Ocampos, and the Argentinean made an instant impact. Nabil Dirar made an impressive run down the right wing, and his pinpoint cross was perfect for the sliding Ocampos, who diverted the ball home against the run of play.
Simon Rolfes and Julian Brandt entered the fray for Lars Bender and Karim Bellarabi, in an attempt to level the game, but Monaco's hearty defence were as strong as ever. Drmic went closest in the final ten minutes when his header went off target, but they couldn't force the equaliser.
Schmidt will no doubt be lamenting missed chances, 18 shots went by for Leverkusen, with just four hitting the target, while Monaco initiated the perfect smash and grab with their only shot on goal.
Monaco go into the final group game now only needing a draw to qualify, but Leverkusen will only ensure top spot if they manage all three points in Portugal, as they travel to Benfica - who have already been eliminated.
