Felix Magath's side capitalized on Bayern Munich's 2-2 draw at Hoffenheim to open a two-point gap with the holders, one week before the finale.
Wolfsburg are now sole leaders with 66 points before they host mid-tablers Werder Bremen next weekend.
Bayern share second spot with Stuttgart, who beat Energie Cottbus 2-0, courtesy of goals from Thomas Hitzlspeger and Cacau.
Incredible Partnership
In Hannover, strike partners Edin Dzeko and Grafite produced another impeccable performance for Wolfsburg at AWD Arena, bagging a hat-trick and a brace respectively.
The duo maintained their dominance for goals in the Bundesliga as Brazilian striker Grafite stayed on top of the scoring charts with 26 goals, one ahead of his teammate.
Bosnian striker Dzeko opened the scoring after 14 minutes with an amazing half-volley from 25 yards; a real contender for goal of the season.
Grafite scored two close-range goals before half-time as Dzeko grabbed two second-half headers to conclude the rout.
Bayern Stumble
At Rhein-Neckar Arena, Bayern failed to improve their first-half 2-2 stalemate with Hoffenheim to drop two precious points in their title-defense quest.
Franck Ribery put the Bavarians in front on 16 minutes, but the home side responded through Demba Ba and Carlos Eduardo in the 21st and 28th minutes.
The league's top scorer last season Luca Toni equalized for Bayern just before half-time, but Jupp Heynckes' side couldn’t add more after the break.
Elsewhere, Hertha Berlin succumbed to a goalless home draw with Schalke to drop two crucial points as well and slip to fourth place with 63 points.