Harry Darby was born in Kansas City, Kansas on January 23, 1895. He attended the University of Illinois for engineering and served in the United States Army during World War I. In 1917, Darby married Edith Cubbison (1894-1980). The pair had four daughters: Harriet Gibbson, Joan Edwards, Edith Marie Evans, and Marjorie Alford. Darby served on the Kansas State Highway Commission from 1933 to 1937.

During WWII, Darby established the Darby Steel Corporation in Kansas City, Kansas. The plant created materials for America's military during the war and built most of the Landing Craft Tanks (LCTs) that were used in amphibious invasions. Due to the company's help with the war effort, it was awarded the Army-Navy "E" Award in 1943.

From 1940 to 1964, Darby served as the Kansas National Committeeman for the National Republican Convention. On December 2, 1949, Darby was appointed United States Senator upon the death of Clyde M. Reed. He served in this position until November 28, 1950.

Darby was a friend of General Dwight D. Eisenhower. The pair corresponded until Eisenhower's death in 1969. Darby was a supporter of the Eisenhower Presidential Library, helping to fundraise and attend Library events. Due to Darby's political status, he was invited to and attended many political functions and events, including National Conventions, political rallies, and a delegation trip to Venezuela in 1959. He also received numerous awards and honorary degrees for his work both with his company and as a politician. Darby remained loyal to his farming roots by supporting the American Royal, the Cowboy Hall of Fame, and numerous other farming-related groups throughout his life.

Harry Darby died in Kansas City, Kansas on January 17, 1987.