Homes and buildings within a 1.5-kilometre radius of the site were due to be cleared by 6am Irish time, but some people were still in the evacuation zone well past the deadline as police carried out door-to-door checks.
Local authorities coordinated the evacuation and will attempt to remove the bomb's fuse using a remotely-controlled device.
The British bomb is a 1.4 ton HC 4000 air mine, according to the statement.
About 21,000 people have been ordered to leave their homes and workplaces in the western city of Koblenz as a precaution before specialists attempt to defuse the 500-kilogram (1,100-pound) U.S. bomb on Saturday afternoon. More than 100 patients in healthcare establishments, including newborn infants, have been evacuated, municipal councilor Markus Frank said.
Around 21,000 people had to leave the area in Koblenz as the 500-kilogramme (1,100-pound) bomb was successfully defused, before the fire brigade allowed residents to return to their homes. "I have never seen anything like it".
Shelters have been set up for residents who are unable to go to friends or family during the bomb operation, with food provided. "By offering free entry to all city museums we want to help those affected to spend a few hours without worrying", Frankfurt's Mayor Peter Feldmann said in a statement.
The evacuation is the biggest since the war ended in 1945.
The bomb was discovered on a building site last week and around 60,000 people were ordered to leave their residences in what was Germany's biggest evacuation since the war.
The bomb was found during construction in an upscale area.