Talismanic captain Vincent Kompany has already left the Etihad, midfield maestro David Silva is going at the end of this season and all-time leading goalscorer Sergio Aguero is expected to depart when his contract runs out in 2021.
The three players were pivotal to City's rise and have been part of all four of the club's Premier League triumphs between 2012 and last season.
The task for Guardiola, whose side look unlikely to defend their Premier League title, is to find players who are good enough to repeat those achievements.
"We cannot deny how important these names have been for the club," said the Catalan ahead of Sunday's Premier League match at Aston Villa.
"Vinny is unique, Sergio is unique, David too. These kinds of players are incredible.
"But this club has the duty and obligation to find the best replacements for all of them and as quickly as possible and to anticipate it.
"You have to move on and it has to happen. But knowing how important they were, they helped us to be the club we are now."