USS Paul Hamilton intercepted a drug-smuggling fishing vessel in the Gulf of Oman worth $42 million.
The ship was supporting the Combined Task Force 150, a multinational naval collaboration comprising 38 countries.
The crew members identified themselves as Iranian nationals.
Other international naval units have previously seized illegal drugs worth an estimated street value of $1 billion.
CTF 150 carries out maritime security checks and counter-terrorism missions in the Indian Ocean and Gulf of Oman.
The Combined Maritime Forces is the largest multinational naval partnership worldwide.
The successful interdiction highlights the importance of having a strong naval presence in the Middle East.
The USS Paul Hamilton and other naval units' efforts counter drug trafficking and other illicit activities in the region.