The massive bust amounts to more than $1bn (£796.3m) worth of cocaine, which authorities seized from a large ship at the Packer Avenue Marine Terminal at a port in southern Philadelphia.
“This amount of cocaine could kill millions — MILLIONS — of people,” US Attorney William McSwain said in a statement confirming the bust.
Members of the crew for the vessel where the cocaine was seized have been arrested and face federal charges. Their identities have not yet been released.
The drug seizure is the latest in a series of large cocaine busts along the east coast of the United States.
In a March bust in Philadelphia, drug dogs sniffed out 1,185 pounds (538 kilograms) of cocaine worth about $38m (£30.3m) — at that time the city’s largest seizure of the drug in more than two decades.
In February, customs agents seized 3,200 pounds (1,451 kilograms) at the Port of New York and New Jersey with a street value estimated at $77m (£61.3m).
That was the largest cocaine bust at the ports since 1994.
Television footage of the latest seized ship in Philadelphia showed its name as MSC Gayane. Online ship trackers said it sails under the flag of Liberia and arrived in Philadelphia after 5:00 am on Monday.
“This is one of the largest drug seizures in United States history,” Mr McSwain wrote.
Other reports have described the seizure as “the largest drug seizure in the history of the Eastern District of Pennsylvania.”