His training in art began with instruction from the drawing-master Pietro Ancora and an apprenticeship to Thomas Wilson, a well-connected painter of signs and coaches in Philadelphia.

Neagle served as Director of the Pennsylvania Academy of the Fine Arts, and was also a founder and president (1835–43) of the Artist's Fund Society of Philadelphia.

[2] Neagle's sitters included society figures, politicians, professionals and merchants, all of whom he treated with an incisive attention to psychology and an often dazzling brushwork derived (by way of Sully and Sir Thomas Lawrence) ultimately from van Dyck.

His most impressive works are, arguably, the full-length allegorical Portrait of Henry Clay (Union League, Philadelphia), and the unconventional and brutally heroic Pat Lyon at the Forge (Pennsylvania Academy of the Fine Arts).

[5]: 190  His papers are housed at the Historical Society of Pennsylvania, which hosted a retrospective exhibition of his work in 1989 (with scholarly catalogue by Robert Torchia).