Three members of the Bow Mariner's crew were confirmed killed in the explosion around 6pm (23:00 GMT) on Saturday about 80km off the Virginia coast, Coast Guard spokesman Petty Officer Donnie Brzuska said in a statement.
Six others from the crew of 27 were rescued by helicopter and taken to a hospital in Norfolk, Virginia.
The 174-meter-long tanker was carrying more than 13.25 million litres of industrial ethanol from New York to Houston, Brzuska said.
The ship's owners, Norwegian-based Odfjell, said in a statement the company was "deeply saddened by this tragic accident that has caused loss of life."
Twenty-four of the crew were Philippine nationals and three were Greeks. Officials in Manila said two of those confirmed dead and the six injured were Filipino.
Brzuska said two Coast Guard cutters and several aircraft were searching the area where the Bow Mariner sank for survivors.