Another efficient display from the reigning champions at Craven Cottage allowed them to edge above Liverpool and back to the summit.
Bernardo Silva broke the deadlock against relegation-threatened Fulham inside five minutes, before Golden Boot leader Sergio Aguero doubled City’s advantage in the 27th minute.
The hosts posed little threat from that point, with the Blues wrapping up a 12th successive success in all competitions – including their Carabao Cup final penalty shootout win – with the minimum of fuss.
City are now a point clear of fellow title chasers, while also being through to the semi-finals of the FA Cup and last eight of the Champions League.
Guardiola is, however, adamant that a clean sweep of major honours is not dominating the thoughts of those at the Etihad Stadium, telling BBC Sport: “We don't think too much about what people say about the quadruple.
“We are going to do everything to win. No matter the next competition, we will win the game.”
Guardiola was pleased with the latest performance put in by his City side, as they slipped seamlessly back into their groove after the international break.
He added to Sky Sports: “Our first 15-20 minutres was one of the best of the season. We played with incredible spirit, we could have scored more. After the goals we controlled it.
“It was an incredible result after the international break and having played away. We did what we should do.
“At the end of the match, maybe the players were tired. We will be back in our rhythm.
“After the break playing at home is different to playing away. Always you have doubts about how they're going to react.
“It's important to have the rhythm. Kevin [De Bruyne] we wanted to give 90 minutes but maybe there was tiredness in his legs. We will not win the Premier League with 11 players.”
City’s fate is in their own hands when it comes to the Premier League crown, with the Blues having now played the same number of games as Liverpool – although the Reds will be back in action on Sunday against Tottenham.
Guardiola is pleased to be leading the way once more, but is aware of the need to retain full focus in what is shaping up to be a dramatic sprint to the finish across multiple competitions.
He said: “Liverpool and Man City have done incredible so far so deserve the credit. We will have 80 points with six games to play if we win next week.
“Enjoy the moment and dream to win another game.”