Scarlatti studied first with his father, Alessandro Scarlatti, and later with the Italian composer Francesco Gasparini. Scarlatti first attracted attention by his revision (1704) of the opera Irene by the Italian composer Carlo Francesco Pollarolo. 

In subsequent years Scarlatti lived in Rome, Naples, and Lisbon and frequently toured Europe as a traveling virtuoso. In 1729 he was summoned to the Spanish court at Madrid, which remained his residence for the rest of his life.

Scarlatti was a founder of the modern school of keyboard technique; he was the first composer to call for such devices in performance as arpeggios, the rapid repetition of a single note, and the crossing of hands. His keyboard compositions, entitled sonatas, are all short pieces. About 550 of these have been preserved; many have a recognizable Spanish flavor. Scarlatti also composed several operas, religious music, and instrumental works.