Before this meeting at the Bernabeu, City and Real Madrid had met 15 times in the Champions League, with results split evenly between wins, losses and draws.
Guardiola must now inspire one of the greatest comebacks of his reign if City are to maintain their interest in Europe's elite competition.
It all started well, with Jeremy Doku posing an early threat to Trent Alexander-Arnold, but once City conceded the first goal, which they will regard as soft, Real grew in confidence as they were roared on by their followers in this magnificent arena.
The hosts ensured Erling Haaland was anonymous, although the Norwegian forward was also starved of the service he usually thrives on.
Guardiola selected a side full of attacking intent, but City were done as Real raced through an open midfield and picked holes in their defence.
City had their opportunities, but faced the usual barrier of Courtois, especially when he miraculously saved with his leg after O'Reilly robbed Thiago in the area.
The fact that they had their chances will give City hope of mounting a comeback in the second leg, but this was a hugely disappointing loss and the experienced Champions League campaigners of Real Madrid will feel quietly confident of progress.
