Australian Robbie Kruse drilled the ball home on the stroke of half-time via a deflection off Hamburg's Michael Mancienne for his second goal this season after a mistake by Heung-Min Son.
Substitute Stefan Reisinger added another goal midway through the second half, taking advantage of a sleepy Hamburg defence to shake off three players with a fine solo effort and beat keeper Rene Adler from eight metres.
Hamburg, who were undefeated in their last four away games, lost Netherlands playmaker Rafael van der Vaart after 32 minutes with a thigh injury. Mancienne also had a goal disallowed for offside.
The game started with a slight delay after Hamburg fans lit flares in the stands.
The win lifted Duesseldorf into 13th place on 14 points, while Hamburg, who have yet to enjoy a good run this season, are stuck in ninth place on 17.
Leaders Bayern Munich, eight points clear, take on Hanover 96 on Saturday while second-placed Schalke 04 host Eintracht Frankfurt, who are in third spot level with them on 23 points.