Bellini ran the most important painting workshop in Venice for over half a century. Whether he was the son or the younger brother of Jacopo Bellini has been debated by scholars since Daniel Maze challenged the traditional assumption; what is not debated is that by the 1470s, Giovanni had surpassed everyone in the family. His older brother Gentile was more famous during their lifetimes, but that ranking has been reversed for centuries.

His brother-in-law was Andrea Mantegna, who married Jacopo's daughter Nicolosia. The two men influenced each other constantly: Mantegna's hard, sculptural line pushed Bellini toward precision, while Bellini's instinct for colour and atmosphere gradually softened Mantegna's edges. The dialogue between them is one of the most productive in Renaissance art.

He transformed Venetian painting by introducing oil glazes over tempera, a technique he adapted from Antonello da Messina after Antonello visited Venice in 1475. The new method allowed him to build up translucent layers of colour that captured the specific quality of Venetian light: soft, diffused, reflected off water. Before Bellini, Venetian painters worked in the dry, linear style of the rest of Italy. After Bellini, Venice had its own tradition.

Titian and Giorgione both came through his workshop. Titian may have caused him some annoyance; their professional relationship was complicated. But Bellini was painting into his eighties, still the official painter of the Venetian Republic, and still producing work that held its own against pupils forty years younger.

When Albrecht Durer visited Venice in 1505, he said Bellini was very old but still the greatest artist of them all.