The authors agree that this surname is of Greek origin and derives from the adjective agathós / agathē, meaning "good". The root is central to Greek moral philosophy and its use as a personal name spread through Christianisation, especially through the cult of Saint Agatha of Catania, a 3rd-century martyr, a figure much venerated in eastern Sicily. The name continued in Latin as Agatha or Agathe, and from there passed into use as a surname.

E. De Felice notes that the surname is widespread mainly in southern Italy, with special presence in Sicily —where it also appears in the variant D'Agata— and in the area of Naples, where the altered form Agatiello exists. He stresses that in Catania the name and surname reach their greatest frequency, in direct correspondence with the popular cult of the saint.

F. Miranda classifies it as a patronymic and extends its geographical distribution to regions such as Tuscany, Lombardy, Lazio, Piedmont, Emilia-Romagna, Campania, Liguria and Calabria. He also records several variants: Agate, Agatelli, Agatello, Agatiello and D'Agatti, which would derive from hypocoristic forms —affectionate or diminutive, also dialectal— of the Latin cognomen Agathius.

V. Blunda specifies that the surname originally functioned as a moral adjective applied to a female ancestor, thus underlining its descriptive character of personal virtue before becoming a surname.