Marco Cornaro's first marriage was to Giovanna Scrovegni of Padua, with whom he had three sons and two daughters. His second marriage was to a woman named Caterina about whom little is known other than her low social status made his later election to the doge difficult. Cornaro acquired his own wealth through trade with Egypt. He also followed both military and political careers in the service of the Republic, leading troops at sea and on the mainland. He served as ambassador to Emperor Charles IV and Pope Clement VI, and was also a member of the Venetian delegation to the election of Pope Urban V in Avignon.
Cornaro was instrumental in the discovery and suppression of the attempted coup d'etat in 1355 by the then doge Marino Faliero, who intended to declare himself prince of Venice. Following the dissolution of the plot and execution of the conspirators, Cornaro was briefly made vice-doge before a successor to Faliero could be appointed.
During the two and a half years of his reign, Venice saw no major changes or wars, though it was to lose the islands of Chios, Lesbos and Phocaea to the Republic of Genoa. He was successful in re-establishing Venetian trade with Egypt by convincing Urban V to rescind his prohibition on dealing with infidels. Cornaro ordered the construction of a wing of the Doge's Palace on its side facing San Marco.