Roddenberry developed an interest in aeronautical engineering and soon obtained a pilot's license. He joined the U.S. Army Air Corps in 1941 and flew combat missions in the Pacific theatre with the 394th Bomb Squadron, 5th Bombardment Wing. In all, he flew approximately 89 missions and was awarded the Distinguished Flying Cross and the Air Medal for his service.

On 2 August 1943, Roddenberry was piloting B-17E Flying Fortress serial number 41-2463, "Yankee Doodle", from Espiritu Santo, New Hebrides when it crashed on takeoff due to mechanical failure, killing two crewmen. After leaving military service, Roddenberry became a commercial pilot for Pan American World Airways. He received a Civil Aeronautics commendation for his rescue efforts following a June 1947 crash in the Syrian desert while on a flight to Istanbul from Karachi.

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