He was born in Berlin, son of a vicar, and was married to Margherita de l'Epine who also performed in some of his theatrical productions.
In the year 1710 (memorable for Handel's first appearance among us) a number of the most eminent composers and performers in London [agreed] to concert a plan of an Academy for the study and practice of Vocal and Instrumental Music, which was no sooner announced than it met the countenance and support of the principal persons of rank.
Pepusch remained Director of the Academy until his death in 1752, and had established England as an important location for the study of music history.
For a period of twenty years, Pepusch also directed the musical establishment at Cannons, a large stately home at Edgware, Middlesex, northwest of London.
[2] Amongst English musicologists, Pepusch is considered significant foremost for his teaching role, but is best known for his arrangement of the music for The Beggar's Opera (1728) — to the libretto of John Gay.