The C-2 "Greyhound" transport aircraft came down about 500 nautical miles (925 kilometers) southeast of Okinawa as it was bringing passengers and cargo from Japan to the USS Ronald Reagan aircraft carrier, the Navy said in a statement.
The Reagan was operating in the Philippine Sea during a joint exercise with Japan's Maritime Self-Defense Force when the twin-propeller plane crashed at 2:45 p.m. Japan time. The cause of the crash was not immediately clear and the incident will be investigated, the Navy said.
U.S. and Japanese naval ships and aircraft are searching for the missing. Japan's Defense Ministry said the crash site is about 150 kilometers (90 miles) northwest of Okinotorishima, a Japanese atoll.
The names of the crew and passengers are being withheld pending notification of next of kin.
In Washington, the White House said President Donald Trump had been briefed on the crash.
Trump said in a tweet: "We are monitoring the situation. Prayers for all involved."
The Navy's Japan-based 7th Fleet has had two fatal accidents in Asian waters this year, leaving 17 sailors dead and prompting the removal of eight top Navy officers from their posts, including the 7th Fleet commander.
The USS John S. McCain and an oil tanker collided near Singapore in August, leaving 10 U.S. sailors dead. Seven sailors died in June when the USS Fitzgerald and a container ship collided off Japan.
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