The execution-style shootings, in the city of Duisburg, happened near an Italian restaurant, where the victims had been celebrating a birthday.
VIDEO: City in shock
Police said the dead, all of whom were shot in the head, were aged 16 to 39. They were found in, or lying next to, two parked vehicles.
It is thought the men — who included two brothers — were caught up in a feud between two Mafia families in southern Italy’s Calabria region.
They had been marking the 18th birthday of one of the victims at a local pizza restaurant, where some of them worked, in the hours before they were killed.
A passer-by called the emergency services after hearing shots fired in the early hours of Wednesday morning, local time.
Five of the victims were dead by the time police arrived. The sixth died on his way to hospital, without giving any clues as to the motive for the bloodbath.
Heinz Sprenger, the officer leading the German police investigation, said all six victims had multiple gunshot wounds.
"These men were shot at indiscriminately," he told a press conference, refusing to confirm suspicions of Mafia involvement.
But Italy's Interior Minister Giuliano Amato appeared on television to suggest the shootings were linked to the Ndrangheta crime syndicate from the Calabrian village of San Luca.
"One of the people killed overnight in Duisburg may be one of the perpetrators of the last crime that took place in San Luca," he said, admitting he feared reprisals as a result of the feud.
Italy's deputy director of police, Luigi De Sena, said such killings in a foreign country were unprecedented.
"This would be the first time it has happened in a foreign country,” he said. “The Calabria Mafia has a significant presence in Germany but until now they have always tried to keep a low profile."
Detectives are hunting two people spotted running away from the scene, and a car seen speeding off shortly afterwards.
They have sealed off the area, and are checking CCTV camera footage from nearby buildings.