He was the grandson of Alfred Cowles, Sr., who was a founder of the Chicago Tribune. His father, Alfred Cowles, Jr. (1865–1939) managed and directed the Chicago Tribune from 1898 to 1901 and the American Radiator Company. His mother was Elizabeth Cheney (1865–1898). His parents lived at 1130 N. Lake Shore Drive in Chicago, Illinois. Alfred Cowles III had three siblings: Knight Cheney Cowles (born 1892); John Cheney Cowles (born 1894); and Thomas Hooker Cowles (born June 6, 1895) who married Barbara Granger, daughter of architect Alfred Hoyt Granger.