It was Germany's biggest Evacuation since World War II.
Residents were ordered to leave after the unexploded 1.8-ton British device was found during construction work in a wealthy suburb of the city.
Police used a helicopter with heat-sensing cameras to ensure the evacuation zone, which covers a radius of around one mile, was completely clear.
The authorities had threatened to use force against anyone who refused to leave after warning the bomb was big enough to destroy an entire city block.
The fire service helped around 500 elderly people to leave their care homes. Emergency crews also evacuated babies and intensive care patients from two hospitals.
The evacuation area included Germany's central bank, where the country's gold reserves worth in the region of €59bn (£54bn) are stored.
Displaced Frankfurt residents found shelter at a collection centre
After hours of delay as police struggled to clear the scene, bomb disposal experts finally managed to disarm the device late in the day.
They used a special system to unscrew the bomb's fuses from a safe distance. If that had failed, they would have cut the fuses with a water jet.
Police then began lifting the evacuation order, giving priority for patients to be brought back to their hospital wards.
Many of those who had been forced to leave were offered space in a temporary centre at the site of Frankfurt's trade fair.
Some of the city's museums had offered free entry to displaced residents.