This is a typically Venetan surname, originating from Dosoledo, in the Comelico Superiore (province of Belluno), where it is documented from the 14th century. From there it spread to other localities of the Comelico, in particular to Presenaio and Santo Stefano di Cadore. The sources agree in placing its area of greatest concentration in the Cadore and the Comelico, within the province of Belluno.

As for the etymology, the sources propose different interpretations. It is considered that the most probable explanation derives the surname from the medieval personal name Zandone or Zandon, a Venetan augmentative form of Zane —a Venetan dialectal variant of Giovanni—, with the affectionate diminutive suffix -ella, characteristic of the formation of surnames in Veneto. Under this reading, the surname would be equivalent approximately to "the little family of Zandone".

E. Rossoni proposes a different etymology: the surname would derive from the expression Zanni di Donella, that is, "Gianni son of Donella", from which the contracted form Zandonella would have arisen. Rossoni documents it in a deed of 1700 coming from the Comelico Superiore area.

The surname does not figure as an autonomous entry in the classic Italian onomastic repertoires, so both etymologies must be considered indicative. The graphic variant Zyandonella, with an initial Y, is unusual in Italian and is probably a deformation arisen at the moment of migratory civil registration.