Giuliano Amato, the Italian interior minister, said the shootings appeared to be the latest chapter in a long-running dispute between involved two mafia clans in Calabria, home to the 'Ndrangheta organised crime group.
Police found the six in, or lying next to, two vehicles near the city's train station after a passer-by heard shots at about 2:30am local time (0030GMT).
Five were already dead and the sixth died on the way to hospital.
Heinz Sprenger, head of the murder commission, said: "We are exploring all possibilities, we are excluding nothing. There were many shots and shot wounds."
Italians are Germany's second biggest immigrant group after Turks. Many from the poor south came to Germany as "guest workers" after World War II and helped fuel the country's economic boom.
About 540,000 Italians live here and are mostly well integrated. At the end of 2006, about 3,500 Italians lived in Duisburg, a city in Germany's industrial heartland, the Ruhr, that has been hit by high levels of unemployment.
The attack in a foreign country is unprecedented and Italian investigators said they feared a bloody riposte by victims' relatives in keeping with the tradition of vendetta.
"We are now trying to prevent a similar tragedy [in Calabria]," Amato told a news conference.
The shootings took place close to an Italian restaurant called Da Bruno where a birthday celebration had taken place.
All the victims either worked at the restaurant or had some connection with it, Sprenger said.
The victims belonged to one of two rival clans based in the town of San Luca.
Their simmering feud began in 1991 and has escalated in the past eight months. Overall 15 people have been killed.
The 'Ndrangheta has outgrown its more famous Sicilian counterpart, the Cosa Nostra, thanks to clan loyalties ensured by blood relationships and arranged marriages, and is now the leading organised criminal group for drug trafficking.
"This was an attack to assert power. It is not just the clan that comes out stronger, it is the 'Ndrangheta as a whole," said Alberto Cisterna, a mafia national prosecutor.
Italian investigators said the 'Ndrangheta was well established in Germany but has traditionally kept a low profile.