Wolfsburg's victory over Nuremberg on Saturday had seen them briefly occupy fourth place in the standings, but Leverkusen overcame the challenge of the capital club at the BayArena to reclaim pole position in the race for Europe's elite tournament by a point.
Less than a minute elapsed before the hosts got off to the ideal start through Stefan Kiessling, who rose highest to plant his header past Thomas Kraft.
Anis Ben-Hatira came within the width of the woodwork from leveling matters after being denied by the crossbar, before Sascha Lewandowski's men doubled their advantage moments later.
From the counter-attack, Bayer broke and found their second of the afternoon as Julian Brandt curled beyond the reach of Kraft on 24 minutes.
Both sides struggled to create the goalscoring opportunities necessary to add to their respective hauls, as Leverkusen held out to secure Lewandowski's first win as boss since replacing Sami Hyypia earlier in the week.