Darrell McClure was born in Ukiah, California, but moved to San Fransisco at age nine. His mother pushed him to develop his artistic talent, so the studied at the California School of Fine Arts for two years. McClure got his first professional jobs in 1920 at some animation studios. This didn't turn out well, so McClare became a seafarer for a while.
A reunion with a fellow Californian, James Swinnerton led to McClure taking on a job at King Features Syndicate as an apprentice artist. After working on several of the King Features productions, Darrell McClure was assigned to his own series, 'Vanilla and the Villains' (1928) and 'Hard Hearted Hicky' (1930), but both were short-lived.
In 1930 Darrell McClure took over the artwork of Brandon Walsh's 'Little Annie Rooney' from Ben Batsford, who had taken over from Ed Verdier in 1929. McClure left the 'Little Annie' Sunday page in 1933 to start a Sunday page of his own, 'Donnie'. Although McClure could use all his knowledge of the sea in his series, this comic also didn't turn out well, so he went back to 'Little Annie Rooney'.
During World War II, McClure also drew 'Ahoy McCoy' for the military magazine All Hands. After retiring from 'Little Annie Rooney' in 1966, McClure focused on painting naval sceneries and doing illustrations for Yachting Magazine.