Aguero has been with Manchester City since 2011 after joining the Manchester based club from Atletico Madrid.
Guardiola said Brazil forward Gabriel Jesus has the potential to replace the 31-year-old, who has 18 months left on his current deal, but insists it will be very difficult to have the same impact as Aguero.
“[Replacing Aguero] will be one of the toughest [jobs],” the 48-year-old said.
“Sergio is irreplaceable. We have another incredible striker in Gabriel [Jesus] and maybe another one will come when Sergio leaves, but he is irreplaceable.”
The former Barcelona and Bayern Munich manager recalled Aguero’s famous title-winning goal against QPR in 2012.
“The most important moment of this club - more important than when this club hopefully wins the Champions League - is when Sergio scored that goal against QPR.”
“That moment is much better than four titles in one season or whatever and he was the guy.
“Sooner or later it will happen, he’ll decide when [he leaves]. I’m sure the club will be ready to try to find the guy to replace him, but of course it will not be easy.”
He added: “I’ve never seen such a big star like him be so humble.”
“So funny, and it is a joy to work with him and how he accepts my decisions when it sometimes doesn't work for him.”
