He was born on the island of Burano in the Venetian Lagoon, and as a result, he became known as Il Buranello. His first attempt at opera, La fede nell'incostanza ossia gli amici rivali (1722), was a spectacular failure, having been hissed off the stage. He subsequently studied music with Antonio Lotti, and after a brief period in Florence working as a harpsichordist, returned to Venice for another attempt at opera. This time, his opera seriaDorinda (1729) was a success and launched his theatrical career.
In 1740, he was appointed music director of the Ospedale dei Mendicanti, and he worked at St. Mark's in Venice from 1748, being appointed maestro di cappella (considered Venice's top musical post) there in 1762. He lived and worked for most of his life in Venice, though from 1741 to 1743 he worked in London, and from 1765 to 1768 he worked for Catherine the Great in St. Petersburg.
His first opera buffa was L'Arcadia in Brenta (1749). This was also his first collaboration with librettistCarlo Goldoni, with whom he produced a number of operas. These works were very popular, with Il filosofo di campagna (1754) a particular success. Goldoni's libretto Il mondo della luna, first set by Galuppi, was later used by a number of other composers, including Joseph Haydn and Giovanni Paisiello. Subsequent operas include L'amante di tutte (1760) and I tre amanti ridicoli (1761), written on libretti by the composer's son Antonio Galuppi, who wrote under the name "A. Liteo."
In his later years, his operatic output decreased somewhat. Among his nonoperatic works are a large number of pieces for harpsichord and several oratorios. By the time of his death, in Venice, Galuppi was one of the best-known and most respected figures in the Venetian musical establishment. A requiem mass was held in his memory at St Mark's. His pupil, Andrea Adolfati, was also a successful opera seria composer.
At least two sacred choral works by Antonio Vivaldi have been attributed[clarification needed] to Galuppi, a Beatus Vir and a Nisi Dominus.; musicologist Janice Stockigt believes that a Dixit Dominus might be another such work.