Many theories on how the particular name Vin Santo or holy wine came to be associated with this style of wine in Italy.

The most likely origin was the wine's historic use in religious Mass, where sweet wine was often preferred. One of the earliest references to a vinsanto wine come from the Renaissance era sales logs of Florentine wine merchants who widely marketed the strong, sweet wine in Rome and elsewhere. Eventually the term vinsanto became almost an umbrella name for this style of wine produced elsewhere in Italy.

Other, likely apocryphal, stories on the name's origin attributes its naming to the work of a 14th-century friar from the province of Siena who would use the leftover wine from Mass to cure the sick. The miraculous healing became associated with the santo or holy wine and the name Vin Santo was allegedly born.

Another 14th century story involving John Bessarion, a patriarch of the Greek Eastern Orthodox Church. According to legend at the Ecumenical Council of Florence of 1349 a local Florentine wine called Vin Pretto (pure wine) was served. After trying the wine, Bessarion is said to have liked the wine and remarked that it was like Xanthos, alluding to the famous straw wine of Thrace, (though some sources said he described the wine as Xantho or yellow).

The Florentine locals thought they heard the patriarch describe the wine as Santo and they accordingly started promoting the wine as a holy wine.

Another theory for the name association often touted is the tradition of starting fermentation around All Saint's Day and bottling the wine during Easter week.