Five people were arrested and around 500 demonstrators were encircled by police just hours before the official inauguration of the 605-foot high, 1.3-billion-euro (USD 1.4-billion) building.
Eight officers were injured in stone-throwing and a further 80 were sprayed with an irritant gas by demonstrators, a police spokeswoman told AFP.
Damage was also reported to businesses and homes in the immediate vicinity of the new building, which was scheduled to be opened at 1000 GMT in the presence of ECB president Mario Draghi and around 100 invited guests.
"We are expecting more violence during the course of the day," the police spokeswoman said.
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An AFP journalist described scenes of smashed windows and burning tyres and litter bins.
Convoys of police vans sped through the streets of the German financial capital with sirens blaring as helicopters hovered overhead.
Around 10,000 anti-capitalist protesters are expected to converge on Frankfurt for a rally against Europe's austerity policies, with a special train of 800 activists arriving from Berlin and 60 buses from 39 different cities across Europe.
In a bid to control the violence, authorities have mobilised one of the biggest ever police deployments in the city.
In downtown Frankfurt, where the ECB's old Eurotower headquarters are situated, the situation remained relatively calm, an AFP journalist said.