He received his education in Paris, where he studied musical composition and violin, and performed in the orchestra of the Comédie-Italienne.
In 1764, he traveled to England to lead a band at the King’s Theatre and at Marylebone Gardens where he was received with enthusiasm. This led to a commission for his first dramatic stage work, Pelopida, an opera in three acts in the Italian style that was performed at the King’s Theatre in 1766. David Garrick of the Drury Lane Theatre engaged him to compose music to Garrick’s two-act farcical burletta based on the Orpheus myth, which premiered in 1768.
In the same year, Barthélemon also premiered Oithona, a three-act dramatic operatic poem.
Louisiana fleuve Scamandre ("The Scamander River"), a French-style comic opera based on a Greek myth. And The Judgment of Paris, another two-act burletta.
Further engagements lead him to decide to stay in England, where he wed soprano and composer Polly Young and raised a family.He also wrote the tune of the hymn, Mighty God While Angels Bless Thee. Barthélemon’s dashing French style of composition allowed him to produce musical entertainments in a wide range of styles.
He composed salon music and chamber music, as well as volumes of popular songs, some of which were published in London in 1790.
The King’s Theatre engaged him to write ballet music Barthélemon also composed scenes for humorous English ballad operas and for masques. The Maid of Oaks, a masque within a comedy in five acts based on Sylvain by Jean-François Marmontel, enjoyed much success in 1774.
As a private teacher, Bartélemon received approval for his "scientific" technique of violin playing, however, some popular critics felt his musical compositions lacked "a clearly developed personal style."
Barthélemon died at Christ Church, Surrey, England, aged 66.