Artjoms Rudnevs brace was enough to inflict Hoffenheim their fifth loss in a row and the tenth of the season in the German Bundesliga.
Hoffenheim caretaker Frank Kramer was unable to return with the team to winning ways as Rudnevs two strikes ensured Hamburg's sixth place in the standings with the 2-0 victory, reports Xinhua.
Hoffenheim staged a dominant start with a couple of chances in the opening period but as the match progressed Hamburg took control and opened the scoring in the 27th minute.
Rudnevs caught Hoffenheim goalkeeper Koen Casteels flatfooted when he headed over him into the left corner.
The hosts nearly added another goal to their tally but the crossbar denied Tolgay Arslans powerful long-range effort.
Nevertheless, Hoffenheim were unable to respond to Hamburg. Rudnevs punished Hoffenheim's lack of aggressive play in the 74th minute.
The Latvian utilised a failed clearance attempt by Sebastian Rudy to volley home from 11 metres.