Zuccarelli apparently began his artistic training very early with Paolo Anesi and later worked in Rome with Giorgio Morandi and his pupil Pietro Nelli. After returning briefly to Florence, he moved to Venice in about 1732 and became associated with the Venetian school.

The facile technique, atmospheric light, and classical pastoral character that typify his picturesque Arcadian landscapes were especially appealing to the English. Zuccarelli visited England twice: at the end of 1752, remaining for 10 years with great success at painting landscapes, and again from 1765 to 1771. He was a founding member of the Royal Academy (1768), and he became one of George III's favourite painters. Zuccarelli had been elected to the Venetian Academy in 1763 and became its president in 1772. In addition to doing much work at Bergamo, he was for a time in Paris, and in the last two years of his life he returned to Rome and afterward to his native Tuscany. In addition to landscape paintings, Zuccarelli executed innumerable drawings, a few religious paintings, engravings, and tapestry designs.