Flick became the first and only Germany head coach to be sacked since the position was created in 1926.
Sporting director Rudi Voeller, who coached the side to a 2002 World Cup final against Brazil, will take over on an interim basis, with a successor to be announced at a later date.
German FA boss Bernd Neuendorf said the sacking was "unavoidable" after the team's recent run of "disappointing" results.
In a statement, Neuendorf said "with a view towards the European championships in our own country, we need a spirit of optimism and confidence", saying the decision was one of his "most difficult so far."
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