It was unclear how long the bomb disposal squad would take to disable the bomb found during construction work on Heidestrasse in the district of Mitte.
Earlier this year, London City Airport, near the Thames in the eastern part of the city, was shut down after a World War II relic, an 1,100-pound German bomb, was discovered during construction work.
Local bus and train routes have been disrupted during the operation while roads surrounding the station have been closed.
Police said the 500kg (1,100lb) bomb, believed to have been made in the United Kingdom, posed no immediate danger but the operation was expected to cause transport chaos in the German capital.
Authorities declared an exclusion zone with an 800-metre radius around the site located just north of the central railway station, a transport hub that on a normal day is used by 300,000 passengers.More news: National Football League schedule 2018: London Games feature firsts as global slate released
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'A short bang - there was a controlled explosion of the detonator away from the bomb, ' the police said.
By Friday afternoon however it was reported that Berlin's main train station had opened again. While the shutdowns were no doubt a headache for these public services and residents for the hours it took to defuse the bomb on Friday, its discovery on Wednesday gave the city a few days to prepare for the shutdown.
An estimated more than 2,000 tons of bombs and ammunition are unearthed in Germany each year. Police went door to door to check the area was empty of people before their specialist team began defusing the bomb.
More than a million of tonnes of bombs landed in Germany during World War II and more than one tenth thought to be unexploded.