The 51-year-old former Bayern Munich midfielder, nicknamed Hansi, assisted national team head coach Joachim Low from 2006 until the country's World Cup success in 2014.
After the tournament in Brazil, Flick took on the sporting director role, but on Monday t he DFB confirmed they had reluctantly accepted his decision to step down two years early.
DFB president Reinhard Grindel told the organisation's website: "Hansi Flick has achieved a great deal in German football over his 10 years at the DFB.
"We let him leave with a heavy heart, but we respect his personal desire."
Flick added: "There are currently no other sporting ambitions, nor are there any problems. The only reason for leaving is my personal desire to concentrate more on my family in the near future. "
Horst Hrubesch, who led Germany to a silver medal at the 2016 Olympic Games, has been named as Flick's temporary replacement.