Matthias Seeger, who has been in office since March 2008, is to be replaced on August 1, Berlin's Tagesspiegel newspaper said, citing sources within the police.
The resignation is thought to be connected to Seeger's contacts to authorities in Belarus, as well as internal conflicts in the police force. No successor has been named yet, but commentators told the paper it was not likely to be his deputy Wolfgang Lohmann.
The federal police's responsibilities includes Germany's borders, and taking care of security at airports, while it also includes the GSG9 special commando unit.
In June, the Bild newspaper speculated that a crisis was brewing in the police force, with sources suggesting that officers were unhappy with Seeger's contacts with the police in Belarus.
The GdP police union stood by him then, saying he was the victim of a smear campaign.
GdP spokesman Josef Scheuring said of Seeger in June, "Unfortunately, and not for the first time, he has to endure a few representatives of the police leadership trying to damage him personally by spreading false rumours."
But those rumours would now appear to be at least partially true.
The resignation completes a miserable month for Germany's security forces, as it comes hot on the heels of no fewer than three resignations of secret service bureau chiefs - head of the federal intelligence service Heinz Fromm, the head of the Thuringia bureau Thomas Sippel, and the head of the Saxony bureau Reinhard Boos.
All three lost their jobs over catastrophic failures in the investigation into far-right terrorist cell the National Socialist Underground, who murdered ten people over a period of eight years.
Fromm's deputy Alexander Eisvogel also lost his job earlier this week, possibly because he was involved in shredding files that were supposed to be supplied to the parliamentary committee investigating the secret service failures.