Two crew members died when an oil tanker connected to an Israeli billionaire was attacked off the coast of Oman, the ship's management firm said.
A Briton and a Romanian were killed amid what the company described as a "suspected piracy incident" onboard the Mercer Street tanker on Thursday.
A US defence official familiar with the details of the incident said the tanker was attacked by an armed drone believed to be operated by Iran.
READ MORE: US military denies American troops in Syria were attacked
Another official said the US responded "to an emergency distress call of an apparent UAV style attack," and that the ship was escorted to port by the USS Ronald Reagan aircraft carrier and the USS Mitscher destroyer.
US Navy personnel, including explosive experts, went on board the vessel to ensure there was no additional danger, the official said.
The incident has been described as a "kamikaze drone attack" in some reports in reference to Japanese pilots who deliberately crashed their armed planes into Allied ships during World War II.
The tanker's crew reported that the drone exploded into its super structure on Thursday, the US official said.
They also reported an unsuccessful attempted drone attack earlier in the day but said that drone fell into the water.
The US military has long noted Iran has drones that operate by flying into targets and exploding on impact. The incident comes amid heightened tensions between Israel and Iran.
The Mercer Street was in the northern Indian Ocean at the time of the incident, travelling from Dar es Salaam in Tanzania to Fujariah in the United Arab Emirates with no cargo onboard, the ship's management firm said.
It is reported to be sailing under a Liberian flag, according to the maritime tracking website Marine Traffic. The vessel is Japanese-owned and managed by Zodiac Maritime, an international ship management company headquartered in London and led by Israeli shipping magnate Eyal Ofer.
Zodiac also confirmed that the ship was under its own power and moving to a safe location with a US naval escort. For now, the US will not say which port the Mercer will go to.
The US State Department said it working was "urgently" to determine what happened.
