Surprisingly, Guardiola opted to ring the changes for the European encounter, making 10 alterations from the team that started Saturday’s disappointing 2-1 Premier League defeat to Newcastle United.
The much-changed City side made a positive start to proceedings, with Nathan Ake forcing Mark Flekken into making a smart reaction stop at the near post. However, Leverkusen quickly gathered their composure from that early scare and stunned their hosts with the opening goal midway through the first period.
The German outfit put together a slick move to work the ball from back to front, culminating with Christian Kofane neatly cushioning a cross down for Alejandro Grimaldo to drill a low strike past James Trafford.
Trailing for the first time in this season’s UCL, City threatened to restore parity in the closing stages of the half when Tijjani Reijnders saw his right-foot shot beaten away by Flekken.
Unimpressed by the events of the first period, Guardiola introduced Phil Foden, Jeremy Doku, and Nico O'Reilly at the break in a bid to inject impetus into a flat performance. However, the substitutes were still finding their bearings when Patrik Schick extended Leverkusen’s advantage within 10 minutes of the restart.
The determined forward got in front of Ake to glance a deft header beyond Trafford from Ibrahim Maza’s inswinging cross to score in back-to-back European games.
That soon prompted Guardiola to summon his star striker, Erling Haaland, who nearly made an immediate impact when he raced through on goal, only to see his effort smothered by the sprawling Flekken.
The Dutchman made another strong stop to keep out Rayan Cherki’s late free-kick and make sure of Leverkusen’s second win of the league phase. Kasper Hjulmand’s charges soar up to 13th spot and to within two points of sixth-placed City, who have lost their unbeaten record in the competition.
Flashscore Man of the Match: Patrik Schick (Bayer Leverkusen)