Germany international Andre Schuerrle's 20-yard missile on the stroke of half-time and a perfect low drive by Stefan Kiessling for his eighth goal of the season made sure Leverkusen bounced back from last week's defeat by VfL Wolfsburg to remain in fifth place on 21 points.
Schalke, on 23 points, had defender Kyriakos Papadopoulos sent off after a second booking late in the game.
Champions Borussia Dortmund, in fourth place, closed to within nine points after a 3-1 home victory over Greuther Fuerth, firing in three goals in the first half with Mario Goetze scoring one and setting up another for their first back-to-back league wins this season.
Eintracht Frankfurt joined Schalke on 23 with a 4-2 victory at home to struggling Augsburg courtesy of two Alexander Meier goals that lifted him jointly top of the scorers' list along with Bayern's Mandzukic.
Hamburg SV hauled themselves up to eighth with a 1-0 home win over Mainz 05 with Hanover 96, in sixth on goal difference, slumping to a 2-1 home defeat by Freiburg.