During the 1860s to 1880s he was a bookkeeper, treasurer, and business manager of the Chicago Tribune of which he was part owner.

Another son, Edwin Jr. (1825–1890), became publisher of The Cleveland Leader newspaper.

Alfred Cowles married Sarah Frances Hutchinson, who was born in 1837 in Cayuga, New York.

They had four children: Edwin (1861–1861), Alfred Jr. (1865–1939), Sarah Frances (1862–1920), and William Hutchinson (1866–1947).

William married Harriet Bowen Cheney, and became a newspaper publisher in Spokane, Washington.