Teenager Toni Kroos, Simon Rolfes, from a penalty, and Eren Derdiyok gave Leverkusen a 3-0 lead in only 34 minutes before Stefan Kiessling added the fourth with his sixth goal of the season midway through the second half.
Leverkusen, still unbeaten, have 20 points from eight games, three ahead of Hamburg SV who visit bottom club Hertha Berlin on Sunday.
Swiss striker Derdiyok added the third six minutes later after exchanging passes with Kiessling, whose headed goal in the 68th minute made him the Bundesliga's topscorer.
Louis van Gaal's team lost 1-0 at Hamburg a week ago and were held 0-0 at home by Juventus in the Champions League on Wednesday.
For the third match running, Van Gaal made the Bundesliga's most expensive signing Mario Gomez start on the bench, although he brought him on at halftime.
Dzeko took his tally to five when he headed in Karim Ziani's cross to save Wolfsburg from a shock defeat at Bochum. His goal came two minutes after the hosts had Japan international Shinji Ono sent off for a high tackle on Josue.
Andreas Ivanschitz, surprisingly left out of Austria's squad again last week, volleyed home, then Burkina Faso striker Aristide Bance headed the second after a mix-up in the Hoffenheim defence.
