Dortmund dropped points for the first time this season earlier in the day, as Per Nilsson cancelled out Marcel Schmelzer's opener to help Nuremberg to a 1-1 draw.
And Pep Guardiola's side quickly underlined their intention to take full advantage at the Veltins Arena, as they raced into a 2-0 lead after just 22 minutes thanks to Bastian Schweinsteiger and Mario Mandzukic.
Schalke had won their last three games in all competitions going into the fixture, keeping clean sheets in all of them, but they were powerless to prevent second-half goals from Franck Ribery and Claudio Pizarro extending Bayern's unbeaten run in the league to 31 matches.
Elsewhere, Third-placed Bayer Leverkusen bounced back from their UEFA Champions League defeat against Manchester United on Tuesday to beat Mainz 4-1.
A Robbie Kruse brace allied to goals from Lars Bender and Stefan Kiessling put Sam Hyypia's men 4-0 up within the hour before Yunus Malli scored a consolation for the home side - who drop to seventh after their third consecutive defeat.
With their win, Hyypia's charges became the first Leverkusen side to amass 15 points from the opening six league games.
Hamburg's first game of the post-Thorsten Fink era began with defeat, as they lost the 99th Nordderby to Werder Bremen 2-0 thanks to goals in either half from Nils Petersen.
While at the other end of the table, an Ivica Olic double helped Wolfsburg come from behind to take all three points against Hoffenheim.
Anthony Modeste opened the scoring for the visitors after 15 minutes before the Croatia international equalised a minute before the break.
And four minutes into the second half, he was on hand again to ensure Wolfsburg moved up into the final UEFA Europa League qualification spot.
Saturday's other game saw Hannover take all three points against Augsburg thanks to a late Szabolcs Huszti penalty.
Paul Verhaegh had put Augsburg ahead six minutes after the break from the spot, but Artur Sobiech equalised nine minutes later and Huszti won it for Mirko Slomka's men a minute from time.
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