He worked for Aldus Manutius, designing the printer's more important humanist typefaces, including the first italic type.
However, as Manutius had achieved a monopoly on italic printing and Greek publishing with the permission of the Venetian government, he had a falling-out with Griffo.
Griffo then went to work for Gershom Soncino, whose family were Hebrew printers.
In 1518 Griffo was charged with the murder of his son-in-law, who had been beaten to death with an iron bar.
His Romans show a degree of abstraction from calligraphy not present in the work of the earlier master Nicolas Jenson, while his italic and Greek types are notably cursive.