Frankfurt city officials say that more than 60,000 residents will have to leave their homes for at least 12 hours Sunday.
On Friday (local time), they called on Frankfurt's residents to clear the area for 1.5 kilometres around the bomb, by 8:00am on Sunday, saying police would be authorised to remove by force anyone who refused to leave.
The bomb is termed a 'Wohnblockknacker' because it could cause a big enough explosion to flatten a city block, a fire department official said.
"This bomb has more than 1.4 tonnes of explosives," Frankfurt fire chief Reinhard Ries said.
"It's not just fragments that are the problem, but also the pressure that it creates that would dismantle all the buildings in a 100-metre radius."
Residents have been asked to leave the area from morning until 6 PM.
The HC 4000 bomb is assumed to have been dropped by Britain's Royal Air Force during the 1939-45 war.
Defusing it will require the biggest post-war evacuation in Germany, with police planning to clear an area including police headquarters, two hospitals, transport systems and Germany's central bank storing $US70 billion in gold reserves.
"We want to avoid not being able to return to these buildings on Monday morning. That would create a very difficult situation for Frankfurt," Mr Ries said.