Andrew Mellow was a native of Pittsburgh. At age 17, in 1872, he left what now is the University of Pittsburgh in his final year to operate his lumber business. In 1882, his father transferred ownership of the Thomas Mellon and Sons family bank to him.

Mellon had the ability to recognize possible growth of certain businesses. He aided them financially and watched them grow into large companies. Among those firms he helped to grow were the Aluminum Company of America (ALCOA), the Carborundum Company, the Gulf Oil Corporation, and the Union Steel Company, which merged with U.S. Steel.

Mellon became secretary of the treasury under President Warren G. Harding and reduced the World War I war debt by nine million dollars. He also served as treasury secretary under Calvin Coolidge and Herbert Hoover. In 1937 he gave his $25 million art collection to the U.S. government and donated $15 million for a museum to house it.