Bruno Labbadia was axed just three days before the return leg in London, with the score still locked at 0-0 after last week’s first-leg stalemate.
Labbadia, who had only been in charge since last summer, paid the price for a poor run of form that culminated in a 5-1 thrashing by Hoffenheim on Sunday.
That result left Hamburg seventh in the Bundesliga and almost certainly needing to win the Europa League to qualify for continental competition next season.
It will only serve to encourage Fulham, however, who have already claimed the notable scalps of Juventus and holders Shakhtar Donetsk at Craven Cottage this year.
Labbadia’s assistant Ricardo Moniz has been handed the reins until the end of the season, and is no stranger to Premier League teams. Moniz worked as a coach at Tottenham under Martin Jol and followed his fellow Dutchman to Hamburg in 2008.