Painter, printmaker, muralist, and educator, Sante Graziani was born March 11, 1920, in Cleveland, Ohio, the son of Tuscan immigrants Giovanni and Cleonice Riccardi Graziani. He attended the Cleveland Institute of Art, graduating in 1941. Graziani then worked for the WPA mural division and painted murals for post offices in Columbus Junction, Ohio, and Bluffton, Iowa, as well as for the Museum of Fine Arts in Springfield, Massachusetts. 

After graduation from the Cleveland Institute of Art, Graziani enrolled in the Yale University art program, receiving his BFA in 1943 before enlisting in the U.S. Army to serve in World War II. He was stationed in the Pacific Theater as Officer in Charge of Arts and Crafts, teaching GIs to draw and paint. When the war ended, Graziani curated a major exhibition at the Imperial Museum of Tokyo. He was also commissioned to design war memorial works by the Belgian and U.S. governments: the first, a monument in Henri-Chappelle, Belgium; the second, a commemorative U.S. stamp.

Upon his return to the United States in 1946, Graziani enrolled in the graduate program at Yale University. He earned his MFA in 1948 and was awarded the Edwin Austin Abbey prize for Outstanding Graduate Art Student. He then taught painting and drawing at the Yale University School of Art from 1946 to 1951, counting Claes Oldenburg among his students. Between 1950 and 1951, he also served as Dean of the Whitney School of Art which is also located in New Haven, Connecticut. In 1951, Graziani began his thirty-year career as Dean at the School of the Worcester Art Museum in Massachusetts. After he retired in 1982, Graziani moved to Hamden, Connecticut, and served as Dean at Paier College of Art. In 1995, he became Dean Emeritus and continued to teach at Paier as well as at the Rhode Island School of Design and Albertus Magnus College in New Haven. He continued to teach until his death on 15 March 2005.

The work of Sante Graziani is represented in the collections of the Brooklyn Museum of Art, New York; the Harvard Art Museums, Cambridge, Massachusetts; the Dallas Art Museum, Texas; the Madison Museum of Contemporary Art, Wisconsin; the Weisman Art Museum, Minneapolis, Minnesota; the Museum of Modern Art, New York; the McNay Art Museum, San Antonio, Texas; and Worcester Art Museum, Massachusetts.

Besides being an educator and artist, Graziani was also passionate about exotic foreign sports cars and motorcycles and was a formula race car driver. He also performed in local orchestras and played five musical instruments.