Alessandro Mastro-Valerio was born in Italy, was educated at the Salvador Rosa Institute in Naples, Italy (1906-1912), and came to the U.S. in 1913.
He settled in Chicago, and after a brief period as a commercial artist, established a portrait studio near the Loop. Among his patrons were the industrialists Harvey S. Firestone and Anheuser Busch. He moved to Ypsilanti, Michigan  in 1919 and received a mural commission to following year from the Ypsilanti National Bank. Mastro-Valerio taught at Ypsilanti Normal College (now Eastern Michigan University) during the summers of 1922 and 1923. He was also on the part-time faculty at the University of Michigan (1924-26) where, after a trip to Italy in 1927, he was appointed to the full-time faculty.
In addition to portraits and murals, his oeuvre includes landscapes, seascapes, and figure studies in oil and watercolor. He is best known for his mezzotint prints, particularly his female nudes. His work helped to revive mezzotint as an artistic medium in the United States. A member of the Ann Arbor Art Associate, the Chicago Society of Etchers, the Society of Design (Associate 1951), he retired from the University of Michigan in 1952.  He died in Ann Arbor in 1953.