Born in Kankakee, Illinois, Harold Gray graduated from Purdue University in 1917. He got his first newspaper job at a Lafayette daily in 1913. He served in World War I as a bayonet instructor. After his discharge, he was employed by the Chicago Tribune. Between 1921 and 1924, he did the lettering on Sidney Smith's 'The Gumps'.
In 1924, Gray came up with a strip of his own: 'Little Orphan Otto' - soon altered to 'Little Orphan Annie', after a poem by James Whitcomb Riley that was being reprinted in the paper at that time. Syndicated by Joseph Patterson's Tribune Media Services, it made its debut on 5 August 1924 in the New York Daily News. The strip was a soap opera about the good and evil in the world, and became very popular during the 1920s.
Gray put his orphan girl and her benefactor Daddy Warbucks through one melodrama after another. He interwove his plots with his conservative and sometimes controversial political philosophy, covering the New Deal, communism, corrupcy and teenage rebellion. Over the years, it has been adapted into radio plays, films and musicals. Especially well-known is the Broadway musical of 1977, that brought forth songs like 'Tomorrow' and 'It's the Hard Knock Life'.
Harold Gray experimented with other strips on the Sunday page, such as 'Private Lives', which gave humorous social commentary; and 'Maw Green', a 'Little Orphan Annie' spin-off. During his career, Gray was assisted by his cousins Ed and Robert Leffingwell. He also helped Ed Leffingwell with the launch of his own Sunday comic, 'Little Joe' in Then he was involved for a while with the strip of his only assistant and cousin, Ed Leffingwell's 'Little Joe', in 1933. Gray was very devoted to his comics work, working hard and diligently. When he died of cancer on 9 May 1968, he had worked on 'Little Orphan Annie' for 45 years. He was eventually succeeded by artist Tex Blaisdell and writer Elliot Caplin.