A youthful prodigy, Clementi was appointed an organist at 9 and at 12 had composed an oratorio. In 1766 Peter Beckford, a cousin of William Beckford, the author of Vathek, prevailed upon Clementi's father to allow him to take the boy to England, where he lived quietly in Wiltshire pursuing a rigorous course of studies. In 1773 he went to London and met with immediate and lasting success as a composer and pianist. The piano had become more popular in England than anywhere else, and Clementi, in studying its special features, made brilliant use of the new instrument and its capabilities. From 1777 to 1780 he was employed as harpsichordist at the Italian Opera in London. In 1780 he went on tour to Paris, Strasbourg, Munich, and Vienna, where he became engaged in a friendly musical duel with Wolfgang Amadeus Mozart at the instigation of the emperor, Joseph II.

In 1782 Clementi returned to London, where for the next 20 years he continued his lucrative occupations of fashionable teacher, composer, and performer. He was a shrewd businessman: in 1799—in the wake of Joseph Haydn's London visits and after Mozart's much-publicized remark that he was a “charlatan, like all Italians,” which together had substantially weakened the market for his music—he cofounded a firm for both music publishing and the manufacture of pianos. Among his numerous pupils were Johann Baptist Cramer, Giacomo Meyerbeer, and John Field. Clementi visited the European continent again in 1820 and 1821. In his later years he devoted himself to composition, and to this period belong several symphonies, the scores of which were either lost or incomplete.

Clementi's chief claims to fame are his long series of piano sonatas, many of which have been revived, and his celebrated studies for piano, the Gradus ad Parnassum (1817; “Steps Toward Parnassus”). His own contributions to the development of piano technique coincided with the period of the new instrument's first popularity and did much to establish the lines on which piano playing was to develop; important traces of his influence may be found in the piano works of Haydn, Beethoven, and even Mozart, as well as the next generation of pianist-composers.