An army hospital, government departments and blocks of flats were among the buildings being cleared on Friday morning to allow experts to diffuse the British explosive.
Police said there 500kg (1,100lb) bomb posed no immediate danger but the operation was expected to cause transport chaos in the German capital.
The 800-metre (2,625 ft) exclusion zone includes Berlin Hauptbahnhof, the city’s main train station, as well as the German finance and transport ministries, foreign embassies, and a museum.
Residents and workers have been told to leave or keep clear of the area from 9am local time (7am GMT). An estimated 10,000 people have been affected, with shelters set up for those forced to leave their homes.
Deactivation of the bomb, unearthed at a building site in Heidestrasse, is scheduled to begin at 11.30am but it is not known how long it will take.
“It depends on how long the evacuation takes and of course the condition of the bomb,” police spokesman Martin Halweg told the Tagesspiegel newspaper.
Transport operators have warned of large-scale disruption to rains, trams and buses.
Berlin’s Tegel airport had warned passengers that flights would be “significantly limited” during the operation, but later said it had arrived at a plan with air traffic controllers to avoid cancellations.
Planes coming in to land at Tegel, which is about 4.5 miles (7km) from Hauptbahnhof, have been told to avoid flying over the area where the bomb was found.
Thousands of live bombs and munitions are still discovered in Germany every year, more than seven decades after the end of the war.
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