Bruno Labbadia, 50, was in his second spell in charge of the club, having taken over in April 2015.
After successfully keeping Hamburg up in the relegation play-offs that season, his first full campaign last year saw him lead the club to a 10th-place finish.
However, Hamburg only have one point from their first five Bundesliga matches this time around, with the last straw proving to be their 1-0 home loss to champions Bayern Munich on Saturday.
Reports in Germany suggest former Hoffenheim boss Markus Gisdol is the favourite to replace him.
Labbadia, whose first spell in charge of Hamburg ended with his contract being terminated in 2010, is the second Bundesliga boss to lose his job early in the campaign after Werder Bremen’s decision to remove Viktor Skripnik.