Giovanni was the second son of Jacopo Dondi dell'Orologio and Zaccarota Centrago or Centraco of Chioggia. His father was a doctor and astronomer, and builder of a large astronomical clock in the tower of the Palazzo Capetanato of Padua in 1344.
Giovanni lived with his father from 1348 to 1359, and shared his father's interest in astronomy and clockmaking. In 1348 he began working on what he called his astrarium or planetarium. He described in detail the design and construction of this project, which was to occupy him until 1364. His manuscripts provided enough material for modern clockmakers to build reconstructions. In 1371 he served as ambassador to Venice, but after the conflict between Padua and Venice in 1372, joined the University of Pavia, and served as diplomat and scholar until his death in Abbiategrasso on 19 October 1388. He is buried at Sant'Eustorgio in Milan.