Federal authorities seized about 16½ tons of cocaine Tuesday from a large ship at the Packer Marine Terminal in Philadelphia, prosecutors said.
They said the haul could have been worth more than $1 billion on the street.
Authorities search a container along the Delaware River in Philadelphia on Tuesday.
The bust is the largest drug seizure in the history of the Eastern District of Pennsylvania, and among the largest ever in the U.S.
The 1,185 pounds of cocaine seized in Philadelphia were valued at $38 million, a CBP spokesperson told NBC 10 Philadelphia.
Federal authorities arrested and charged two of the ship's crewmembers Ivan Durasevic and Fonofaavae Tiasaga.
Several crew members allegedly helped transfer bales of cocaine.
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'This amount of cocaine could kill millions - MILLIONS - of people, ' U.S. Attorney William McSwain said on Twitter.
The drug seizure is the latest in a series of large cocaine busts along the East Coast. The drugs were hidden inside seven containers.
Images broadcast on local television showed vehicles from the US Customs and Border Protection on the wharves of the port, and four agents boarding the large container ship.
Online ship trackers said the vessel detained in Philadelphia sails under the flag of Liberia and arrived in Philadelphia after 5 a.m. Monday. According to VesselFinder.com, in the past month, the ship has docked in Freeport, Bahamas; Cristobal, Panama; Callao, Peru; and Buenoventura, Colomia.
It is unclear whether the drugs seized on Tuesday were intended for the USA or Europe, where the ship was ultimately bound.
The shipping company MSC has been made aware of the find, saying "it takes this matter very seriously" and looks forward to cooperating with the USA authorities.
In order to hook customers, traffickers mix cocaine with the powerful drug fentanyl, a synthetic opioid that is 100 times more potent than morphine and 50 times more potent than heroin.