Antonello was a member of a family of sculptors and artisans, originally from Northern Italy, but active throughout Italy, including Genoa, Florence, and Rome. The family includes his father, Domenico (1449–1492), also a sculptor. Antonello had five sons who were sculptors: Antonio (or Antonino; 1510s-1574), Fazio (1520s-1567), Giacomo (1517–1598), Giandomenico (1503-1560s), and Vicenzo (1527–1595).
One of Antonio Gagini's most notable works is the decorated arch in the Capella della Madonna in the Santuario dell'Annunziata in Trapani which he completed in 1537. Antonello also completed decorative ecclesiastical sculpture in the area of Messina. A large collection of his works including an Annunciation, Madonna with Child, Madonna of the Snow and the Appearance of the Cross to Constantine are now in the Palazzo Abatellis in Palermo. He worked also at the Cathedral of Palermo. Other works were destroyed during earthquakes. He helped train Giacomo del Duca.