Some 54,000 people of a total 80,000 population were ordered to leave their homes at 8 a.m. (2 a.m. ET), said Francesca Cuomo, a press officer at Brindisi City Hall.
This is the first WWII bomb found in the city since 1945, and the evacuation is the largest undertaken in Italy since the end of the war, she added.
The British-made bomb -- which measures more than three feet in length and weighs 500 pounds -- was dropped in 1941.
It had lain untouched until it was found on November 2 by builders working to expand a local cinema.
The bomb was damaged during the operation, making it riskier than previous bomb disposals in Italy, Cuomo said.
People were allowed to return home at 1 p.m. (7 a.m. ET) Sunday after it was successfully removed.
A controlled explosion of the bomb will take place Monday in a sand quarry outside Brindisi, where it was taken on Sunday, said Lt. Col. Vincenzo Lipari of the Italian Armed Forces.
Defense Minister Lorenzo Guerini tweeted that the operation was "particularly complex" and congratulated those involved.
Brindisi's airport, train station, two hospitals and a prison were all evacuated, Reuters reported.
In 2016, a major mountain pass on the Austrian-Italian border was closed so authorities could defuse an unexploded WWII bomb dropped by the United States Air Force.
Italy was bombed by the Allies from 1940 to 1945, with the campaign starting around 24 hours after dictator Benito Mussolini declared war on Britain and France, according to the Centre for the Study of War, State and Society at the University of Exeter, UK.
Unexploded ordnance from WWII is regularly discovered in Europe and beyond.
On Saturday, a bomb was discovered by engineers working on a new sewer in west London. Another was defused in Berlin in April 2018, and another was uncovered at a building site in Hong Kong in February the same year.