Dana was born in Utica, New York. He showed an early interest in science, which had been fostered by Fay Edgerton, a teacher in the Utica high school, and in 1830 he entered Yale College, in order to study under Benjamin Silliman the elder. Graduating in 1833, for the next two years he was teacher of mathematics to midshipmen in the navy, and sailed to the Mediterranean while engaged in his duties. In 1836 and 1837 he was assistant to Professor Silliman in the chemical laboratory at Yale, and then, for four years, acted as mineralogist and geologist of a United States exploring expedition, commanded by Captain Charles Wilkes, in the Pacific ocean. His labours in preparing the reports of his explorations occupied parts of thirteen years after his return to America in 1842.
In 1844 he again became a resident of New Haven, married the daughter of Professor Silliman, and in 1850, on the resignation of the latter, was appointed Silliman Professor of Natural History and Geology in Yale College, a position which he held until 1892. In 1846 he became joint editor and during the later years of his life he was chief editor of the American Journal of Science and Arts (founded in 1818 by Benjamin Silliman), to which he was a constant contributor, principally of articles on geology and mineralogy.
Dana's best known books were his System of Mineralogy (1837) and Manual of Geology (1862). A bibliographical list of his writings shows 214 titles of books and papers, beginning in 1835 with a paper on the conditions of Vesuvius in 1834. His reports on Zoophytes, on the Geology of the Pacific Area, and on Crustacea, summarizing his work on the Wilkes expedition, appeared from 1846 onwards. Other works included Manual of Mineralogy (1848), afterwards entitled Manual of Mineralogy and Lithology (ed. 4, 1887); and Corals and Coral Islands (1872; ed. 2, 1890). In 1887 Dana revisited the Hawaiian Islands, and the results of his further investigations were published in a quarto volume in 1890, entitled Characteristics of Volcanoes.
He was awarded the Copley Medal by the Royal Society in 1877 and the Wollaston Medal by the Geological Society of London in 1874.