After the war, Brinton practiced medicine in West Chester, Pennsylvania for several years; was the editor of a weekly periodical, the Medical and Surgical Reporter, in Philadelphia from 1874 to 1887; became professor of ethnology and archaeology in the Academy of Natural Sciences in Philadelphia in 1884; and was professor of American linguistics and archaeology in the University of Pennsylvania from 1886 until his death.
He was a member of numerous learned societies in the United States and in Europe and was president at different times of the Numismatic and Antiquarian Society of Philadelphia, of the American Folklore Society, the American Philosophical Society, and of the American Association for the Advancement of Science.
At his presidential address to the American Association for the Advancement of Science in August 1895, Brinton advocated theories of scientific racism that were pervasive at that time. As Charles A. Lofgren notes in his book, The Plessy Case, although Brinton "accepted the 'psychical unity' throughout the human species," he claimed "all races were 'not equally endowed,' which disqualified [some of] them from the atmosphere of modern enlightenment." He asserted some have "...an inborn tendency, constitutionally recreant to the codes of civilization, and therefore technically criminal." Further, he said the characteristics of "races, nations, tribes...supply the only sure foundations for legislation, not a priori notions of the rights of man.
Brinton was an anarchist during his last several years of life. In April 1896, he addressed the Ethical Fellowship of Philadelphia with a lecture on "What the Anarchists Want," to a friendly audience. In October 1897, Brinton had dinner with Peter Kropotkin after the famous anarchist's only speaking engagement at Philadelphia. Kropotkin had refused invitations from all of the city's elites.
On the occasion of his memorial meeting on October 6, 1900, the keynote speaker Albert H. Smyth stated: "In Europe and America, he sought the society of anarchists and mingled sometimes with the malcontents of the world that he might appreciate their grievances, and weigh their propositions for reform and change."
In addition, he edited and published a Library of American Aboriginal Literature (8 vols. 1882-1890), a valuable contribution to the science of anthropology in America. Of the eight volumes; six were edited by Brinton himself, one by Horatio Hale and one by Albert Samuel Gatschet. His 1885 work is notable for its role in the Walam Olum controversy.