The record-breaking Argentinian is likely to be on the bench for the reigning Premier League champions visit to Wolves on Friday as he continues his recovery from a thigh problem.
That injury has sidelined the 31-year-old since the end of November and given Guardiola a taste of what life will be like when Aguero’s contract ends next year.
The City manager does not expect to be able to talk Aguero into changing his plans to end his career in his homeland and that will leave Guardiola with the thankless task of replacing a man who has, to date, scored 244 times for his club.
“I’d say it will be one of the toughest (tasks). Sergio is irreplaceable,” said Guardiola.
“We have an incredible other striker in Gabriel Jesus and maybe another one will come when Sergio leaves. But he is irreplaceable.”
Aguero played a pivotal role when City were crowned champions of England for the first time in 44 years when his last-gasp winner against QPR took them to the 2011/12 Premier League title.
“The most important moment of this club, more important than if one day this club wins the Champions League, is the moment when Sergio scored that goal, against QPR to win the first Premier League (2012) after I don’t know how many years,” said Guardiola.
“That moment is much better than four titles in one season or whatever. And he was THE guy. More than anything, more than the goals he has done at this club.
“But sooner or later it is going to happen (Aguero’s departure), he’ll decide when.”
Aguero’s efforts in the three-and-a-half seasons that Guardiola has been in charge at the Etihad have been all the more impressive given many thought the Argentina international would not fit into the Catalan manager’s demanding style of play.
Jesus was seen as an immediate successor to Aguero but the veteran had other ideas and, after leading City to that memorable maiden Premier League title in 2012, has been a central figure during the most successful years in the club’s history.
“He’s responded incredibly well,” said Guardiola.