Piranesi was born in Mogliano Veneto, near Treviso. He studied architecture with his uncle, Matteo Lucchesi. From 1740 he was in Rome, living in the Palazzo Venezia and studying with Giuseppe Vasi, who introduced him to the art of etching and engraving. After his studies with Vasi, he collaborated with pupils of the French Academy in Rome to produce a series of vedute (views) of the city - Prima parte di Architettura e Prospettive (1743) and 1745 Varie Vedute di Roma Antica e Moderna (1745).
From 1743 to 1747 he lived mainly in Venice where, according to some sources, he often visited Giovanni Battista Tiepolo. He then returned to Rome, where he opened a workshop in Via del Corso. In 1748–1774 and created series of vedute of the city which established his fame. He also began the measurement of many of the ancient buildings which would led to the publication of Le Antichità Romane de' tempo della prima Repubblica e dei primi imperatori ("Roman Antiquities of the Time of the First Republic and the First Emperors").
In 1761 he became a member of the Accademia di San Luca and opened a printing facility of his own. In 1767 he was created a knight of the Golden Spur, which enabled him henceforth to sign himself "Cav[aliere] Piranesi". In 1777–78 Piranesi published Avanzi degli Edifici di Pesto, (Remains of the Edifices of Paestum) a collection of views of Paestum.
