City are involved in one of the tightest Premier League title races in years with the Reds, as they lead their rivals by one point with two matches remaining.
The former Barcelona and Bayern Munich boss is no stranger to winning league titles with eight in his top-level managerial career so far, but believes Liverpool have been the staunchest challenger despite facing off against the likes of Borussia Dortmund and Real Madrid in previous campaigns.
"In the league, yes, it is the most difficult one for sure. Every league you win is so nice and it is always difficult, but this one especially so," Guardiola told Sky Sports News.
"And especially where we have come from, getting 100 points and still being there. [It is hard] for athletes to maintain that level for a long time and we have done it again."
Guardiola is aiming to earn back-to-back league titles for the first time in Manchester City's history and believes the club's consistency of challenging is down to winning mentality.
"The biggest [players], when they take a shower after one victory, they are thinking of the next one," he said.
"That is sport. People who come to the Etihad Stadium this season do not come to remember how beautiful we were last season. That is done.
"Next season will be the same. When I am sitting here just remembering what we have done, I will resign immediately.
"Txiki [Begiristain] would say 'you have to change the manager'. The big clubs are always thinking of the next win and the next one."