Despite dominating the game, Hamburg were handed their first defeat of the season thanks to Wolfsburg's deadly duo Dzeko and Grafite.
Though the visitors' goal on the quarter-hour came as a surprise, their goalscorer did not. Peter Pekarik cut out a sloppy Marcell Jansen pass before getting forward to cross. His cutback deflected off Joris Mathijsen's hand and perfectly into the path of Edin Dzeko who found the back of the net.
The catalyst for Hamburg's 27th minute equalizer was a glorious run from Jonathan Pitroipa, who showed Andrea Barzagli a clean pair of heels. Another deflected cross then found its way through to Eric Maxim Choupo-Moting who headed the ball past Diego Benaglio.
Marcel Schaefer was instrumental in Wolfsburg's second as his marauding run forward ended in a wicked cross, which was guided home by Dzeko's strike-partner Grafite.
The Brazilian then sealed the game with a terrific low shot past Rost's near post on 78 minutes after he took on Mathijsen in the penalty box. It was his sixth goal against Hamburg.
Hamburg had started the better of the two sides and had a pair of superb Mladen Petric free-kicks, both beaten away by Benaglio, to show for their early domination.
Frank Rost was called upon on 31 minutes to show all his experience when he came out of his goal to palm away Edin Dzeko's attempted lob over the onrushing veteran.
Ruud Van Nistelrooy was inches away from giving his side the lead on 52 minutes when he just failed to get a touch on Ze Roberto's right wing cross. Less than sixty seconds later, captain Heiko Westermann rattled the post with a fine header.
Die Woelfe had a fantastic chance to score when Frank Rost vacated his goal only to find Thomas Kahlenberg but the Dane could get no power on his shot, much to Hamburg's relief.
However, Grafite proved to be more clinical and his late double salvo killed off a shell-shocked Hamburg side, who could not force even a consolation goal in the closing stages although Barzagli did clear off the line from Pitroipa.
Hamburg face yet another northern neighbor on Saturday evening as they travel to Bremen while Wolfsburg host one of this season's overachievers Freiburg a day later.
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