Authorities say members of the ship's crew have been arrested and charged.
CBS 3 is live at the scene showing law enforcement investigating the ship.
The cargo ship owner Mediterranean Shipping Company said in a statement that it was aware of the incident and that it has a history of working with US law enforcement agencies to help disrupt illegal narcotics trafficking.
This is one of the largest drug seizures in United States history.
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The seizure greatly outranks two other major cocaine smuggling busts in the US this year-1,185 pounds of cocaine were seized at a shipping port in Philadelphia in March, and 1.6 tons were seized at a port in Newark, N.J.in February, the largest cocaine bust at that port in 25 years.
Earlier this year, $77 million in cocaine was seized in Newark when investigators cracked open a shipping container.
The ship was in Chile, Peru and Colombia and Panama over the last month, according to Reuters vessel tracking data.
In a March bust in Philadelphia, drug dogs sniffed out 1,185 pounds of cocaine worth about $38 million - at that time the city's largest seizure of the drug in more than two decades.
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.
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. A 1989 bust in downtown Los Angeles netted nearly 43,000 pounds (19,504 kilograms) of the drug.