Mellon served in the United States Army in both world wars and remained active in the United States Army Reserve, receiving the Distinguished Service Medal and rising to the rank of Lieutenant General.
He is chiefly remembered for his urban renewal efforts in Pittsburgh, undertaken in an unlikely partnership with postwar mayor David L. Lawrence. After returning to the city after World War II, Mellon developed an interest in improving Pittsburgh's severe flooding, pollution, and urban blight. Under the auspices of the Allegheny County Community Development Association, massive demolition and redevelopment projects transformed the city, backed politically by Lawrence and financially by Mellon and his companies. Mellon also used his economic power to push companies and landowners to comply with new regulations.
He married Constance Prosser McCaulley, daughter of a New York banker, in 1936. They had four children: Richard P. Mellon, Seward Prosser Mellon, Constance Barber Mellon, and Cassandra Mellon Milbury. Richard King Mellon was also the primary financial founder of Carnegie Mellon University's Heinz School, then known as the School of Urban and Public Affairs.