With the support of his stepmother and after overcoming the opposition of his father, who wanted him to be a sign painter, Leidy studied medicine at the University of Pennsylvania.

[3] Their marriage was childless, and they eventually adopted an orphaned seven-year-old girl,[4] Alwinia, daughter of the late Professor Franks of the University of Pennsylvania.

[6] Leidy named the holotype specimen of Hadrosaurus foulkii, which was recovered from the marl pits of Haddonfield, New Jersey.

Leidy concluded, contrary to the view prevailing at the time, that this dinosaur could adopt a bipedal posture.

He also described the holotype specimens of Arctodus (A. pristinus), the dire wolf (Aenocyon dirus), and the American lion (Panthera atrox), among many others.

Examining her, Leidy originally reported that she had died in the 1793 Philadelphia yellow fever epidemic, but X-rays taken in 1987 showed that she had buttons on her body that weren't produced until the 1830s.

[23] Today, the Victorian cases and hand-labelled specimens remain almost unaltered since Leidy's reorganization in the late 19th century.

[23] Leidy was also a renowned parasitologist, and determined as early as 1846 that trichinosis was caused by a parasite in undercooked meat.

He was also a pioneering protozoologist, publishing Fresh-water Rhizopods of North America in 1879 – a work that is still referenced today.

Leidy served as a surgeon to Satterlee Military Hospital in Philadelphia during the American Civil War.

In 1907, Edward Anthony Spitzka published a paper of his analysis of six brains at the American Anthropometric Society, including Leidy's.