Chapman returned to the United States in 1804, and established a medical practice in Philadelphia. He gave a private course of lectures on obstetrics in the same year, which proved so popular that, in 1806 at age 26, he was elected adjunct to the Professor of Midwifery at the University of Pennsylvania, and soon thereafter was made chair of Materia Medica. Upon the death of Benjamin Rush in 1813, he was transferred to the chair of Theory and Practice of Medicine (after Benjamin Smith Barton held the post for a brief time. Chapman gained the post in 1815.), which he would retain for nearly forty years, until his retirement in 1850. In addition to his lectures at the University of Pennsylvania, he also gave annual lectures at the Philadelphia Alms House and the Medical Institute of Philadelphia.
Of his published works, the most popular were Select Speeches, Forensic and Parliamentary (1804), touching on both medical and political matters, and Therapeutics (1817), a work on what was then termed materia medica that went through seven editions.