Barbaro served as Venetian ambassador to Mantua in 1443, Ferrara in 1444, and Milan in 1446.
As governor of Brescia, from 1437 to 1440, Francesco Barbaro was able to reconcile the two rival factions of Avogadri and Martinenghi and he attained a great reputation in his defense of the city against the forces of the Duke of Milan, led by Niccolò Piccinino.