After studying medicine for a time, Baird became professor of natural history at Dickinson College in 1845, assuming also the duties of the chair of chemistry, and giving instruction in physiology and mathematics. This variety of duties in a small college tended to give him that breadth of scientific interest which characterized him through life, and made him perhaps the most representative general man of science in America. For the long period between 1850 and 1878, he was assistant-secretary of the Smithsonian Institution, in Washington, D.C., where he encouraged the work of the young naturalists in the Megatherium Club. On the death of Joseph Henry he became secretary. From 1871 until his death, he was also U.S. Commissioner of Fish and Fisheries.
While an officer of the Smithsonian, Baird's duties included the superintendence of the labour of workers in widely different lines. Thus, apart from his assistance to others, his own studies and published writings cover a broad range: iconography, geology, mineralogy, botany, anthropology, general zoology, and, in particular, ornithology; while for a series of years he edited an annual volume summarizing progress in all scientific lines of investigation. He gave general superintendence, between 1850 and 1860, to several government expeditions (including the Pacific Railroad Surveys) for scientific exploration of the western territories of the United States, preparing for them a manual of Instructions to Collectors.
Of his own publications, the bibliography by George Brown Goode, from 1843 to the close of 1882, includes 1063 entries, of which 775 were short articles in his Annual Record. His most important volumes, on the whole, were Catalog of North American Reptiles (1853, with Charles Frédéric Girard), Birds, in the series of reports of explorations and surveys for a railway route from the Mississippi river to the Pacific ocean (1858), of which Dr Elliott Coues says that it exerted an influence perhaps stronger and more widely felt than that of any of its predecessors, Audubon's and Wilson's not excepted, and marked an epoch in the history of American ornithology ; Mammals of North America: Descriptions based on Collections in the Smithsonian Institution (Philadelphia, 1859); and the monumental work (with Thomas Mayo Brewer and Robert Ridgway) History of North American Birds (Boston, 1875-1884; Land Birds, 3 vols., Water Birds, 2 vols).
He died in Woods Hole, Massachusetts, site of the great marine laboratory which as an institution which was largely the result of his own efforts, and which has exercised a wide effect upon both scientific and economic ichthyology.