[5] He was born on 16 December 1944 in Reggio Calabria, where he grew up with his younger siblings Gianni and Donatella, along with their father, Antonio, and dressmaker mother, Francesca.

Like his brother Gianni, he attended Reggio Calabria's Liceo Classico Tommaso Campanella, where he studied Latin and Ancient Greek.

Santo played a leading role in the success of the Versace brand by focusing on communication, organization, productivity, and quality.

He is Chairman of Operation Smile Italy Onlus, an association of doctors and volunteers which deals with children with facial deformities in 70 countries around the world.

[9] Versace is portrayed by Italian actor Giovanni Cirfiera in the second season of the anthology series American Crime Story, which premiered on 17 January 2018.