A native of Portsmouth, Reinagle immediately began teaching and performing music upon his arrival in New York. Reinagle moved to Philadelphia, reviving the City Concerts for the 1786-7 with a series of 12 concerts. The City Concerts featured European works alongside of Reinagle's own compositions. An accomplished teacher in Philadelphia, Reinagle gave piano lessons to George Washington's adopted daughter Nelly Curtis.
In the early 1790s, Reinagle and his business partner Thomas Wignell, an English actor, became an important player in the theatre scene, beginning The New Company that toured between Philadelphia and Baltimore. The company performed works of several genres, from ballet and light opera to spoken and musical plays. In his 15 years with the company, Reinagle composed several pieces for the group, from incidental songs to full-fledged productions. However, due to a fire that destroyed the Philadelphia New Theatre in 1820, most of these works are lost.
When Reinagle died in 1809, he left his oratorio Paradise Lost unfinished.
Reinagle is most famous for his four piano sonatas of 1790, considered by many scholars to be the "finest surviving American instrumental productions of the eighteenth century."