Police will ring every doorbell and use helicopters with heat-sensing cameras to make sure nobody is in the area before they diffuse the bomb, and anyone who refuses to leave would be forcibly removed.
More than 60,000 people have been ordered to leave a radius of 1.5 kilometers - almost a mile - around the site where the 1.8-ton British bomb will be disposed of Sunday.
The police said that the demining works kicked off on the site following the evacuation.
"There're still people surfacing, and they need to be brought out of the evacuation zone", said a spokesman for Frankfurt's firefighting service, adding that this process was "incredibly annoying and time-consuming".
Premature babies and intensive care patients had to be evacuated along with everyone else from two hospitals and rescue workers helped about 500 elderly people leave residences and care homes. Almost 60,000 people are expected to leave their homes on Sunday when the bomb is scheduled to be disposed of.More news: CBP announces contractors for border wall proposal
More news: Drinkwater focused on Blues move
More news: Rohingya people dead after boat sinks off Bangladesh
The HC 4000 bomb is believed to have been dropped by Britain's Royal Airforce in World War II.
In July, a kindergarten was evacuated after teachers discovered an unexploded Second World War bomb on a shelf among some toys.
More than 2,000 tonnes of live bombs and munitions are found each year in Germany, even under buildings.
The 1.8-tonne British bomb, which German media said was nicknamed "wohnblockknacker" - or blockbuster - for its ability to wipe out whole streets and flatten buildings, was discovered on Tuesday during building works.
The brigade's director, Reinhard Ries, told reporters: "The scale of this bomb is overwhelming".