Moore received a bachelor's degree and worked initially with the Miami Herald and Miami Beach Beacon. He later founded the Nassau News Bureau (later Bahama News Bureau) and simultaneously worked for Associated Press (AP) and United Press International (UPI) without the agencies knowing he was with their rival.

He was assistant editor for pulp Argosy and became editor in late 1930. In 1934, he became assistant editor for Cosmopolitan magazine.

In August 1935, he took over writing Flash Gordon (King Features Syndicate) from creator Alex Raymond, and continued writing the strip after Austin Briggs took over the art in 1944. He also scripted Raymond's Jungle Jim (King Features Syndicate).

He subsequently worked for RKO Radio Pictures and Warner Brothers, wrote fiction for Cosmopolitan magazine, and was story editor for MGM and Screen Gems television. His first television scripts were for Captain Video and His Video Rangers.

He was married in approximately 1934 to Isabel Walsh (b. 1911); she became a short-story writer for Cosmopolitan. Their daughter was the novelist Pamela Moore. Don and Isabel divorced in 1946; Don had a second wife, Anne.

Don retired to Venice, Florida in 1969.