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Alejandro Grimaldo and Patrik Schick got on the scoresheet for Kasper Hjulmand's Bundesliga side while the Premier League outfit was unable to find its way past a resolute Leverkusen defence, seeing it lose its first game in European competition this season.

Guardiola made 10 changes from the City side that lost to Newcastle United, with only Nico Gonzalez keeping his place, but the hosts started on the front foot as Nathan Ake and Tijjani Reijnders both tested Mark Flekken.

But it was Leverkusen that went ahead in the 23rd minute, with Christian Kofane laying the ball off for Grimaldo from Ibrahim Maza's cross, and the Spaniard found the bottom-right corner with a first-time strike.

City continued to create chances as Reijnders forced another save from Flekken before the goalkeeper also kept out a deflected cross from Oscar Bobb.

However, the Bundesliga side doubled its advantage early in the second half as Schick powered a header past James Trafford.

Erling Haaland came off the bench but failed to get the better of Flekken, while Rayan Cherki also saw a late free-kick denied by the Dutchman as Guardiola was made to rue his tactical changes.

"I take full responsibility, still I think the players that started were exceptional players but we missed something needed at the highest level. We now have to fight for the next games," Guardiola said after the defeat.

"I have to accept it. If we win it [changes] wouldn't be a problem, so I have to accept it that maybe it's a lot, but I think playing every two or three days we need to [make changes] but seeing the result, maybe it's too much."

Leverkusen defender Jarell Quansah was thrilled at the result, impressive as it was achieved away from home.

"It's an unbelievable feeling [to win at Etihad Stadium] to be honest," he said.

"We needed a lot of character and a lot of fight and grit.

"We know they've got a lot of world-class quality and even the players that started tonight we know they're world-class players playing for their countries as well, so it was always going to be a tough task when they came on. We defended a bit deeper than I would have liked to but glad to get the win."

Leverkusen boss Kasper Hjulmand also called it a night to remember.

"We are so happy with this win, but not only the win but the character the team showed," he said.

"I have great respect for the players, for the team we are. We are building a team here, and I think this night is a night to remember, and it's fuel to our development.

"Of course we had moments where we needed a little bit of luck and a very good keeper tonight."