James interacted with a wide array of writers and scholars throughout his life, including his godfather Ralph Waldo Emerson, his godson William James Sidis, as well as Charles Sanders Peirce, Bertrand Russell, Josiah Royce, Ernst Mach, John Dewey, Macedonio Fernández, Walter Lippmann, Mark Twain, Horatio Alger, Jr., G. Stanley Hall, Henri Bergson and Sigmund Freud.
James spent almost all of his academic career at Harvard. He was appointed instructor in physiology for the spring 1873 term, instructor in anatomy and physiology in 1873, assistant professor of psychology in 1876, assistant professor of philosophy in 1881, full professor in 1885, endowed chair in psychology in 1889, return to philosophy in 1897, and emeritus professor of philosophy in 1907.
James studied medicine, physiology, and biology, and began to teach in those subjects, but was drawn to the scientific study of the human mind at a time when psychology was constituting itself as a science. James's acquaintance with the work of figures like Hermann Helmholtz in Germany and Pierre Janet in France facilitated his introduction of courses in scientific psychology at Harvard University. He taught his first experimental psychology course at Harvard in the 1875–1876 academic year.
During his Harvard years, James joined in philosophical discussions and debates with Charles Peirce, Oliver Wendell Holmes, and Chauncey Wright that evolved into a lively group informally known as The Metaphysical Club in 1872. Louis Menand (2001) suggested that this Club provided a foundation for American intellectual thought for decades to come. James joined the Anti-Imperialist League in 1898, in opposition to the U.S. annexation of the Philippines.
Among James's students at Harvard University were luminaries such as Boris Sidis, Theodore Roosevelt, George Santayana, W. E. B. Du Bois, G. Stanley Hall, Ralph Barton Perry, Gertrude Stein, Horace Kallen, Morris Raphael Cohen, Walter Lippmann, Alain Locke, C. I. Lewis, and Mary Whiton Calkins. Antiquarian bookseller Gabriel Wells tutored under him at Harvard in the late 1890s.
Following his January, 1907 retirement from Harvard, James continued to write and lecture, publishing Pragmatism, A Pluralistic Universe, and The Meaning of Truth. James was increasingly afflicted with cardiac pain during his last years. It worsened in 1909 while he worked on a philosophy text (unfinished but posthumously published as Some Problems in Philosophy). He sailed to Europe in the spring of 1910 to take experimental treatments which proved unsuccessful, and returned home on August 18. His heart failed on August 26, 1910 at his home in Chocorua, New Hampshire. He was buried in the family plot in Cambridge Cemetery, Cambridge, Massachusetts.
He was one of the strongest proponents of the school of functionalism in psychology and of pragmatism in philosophy. He was a founder of the American Society for Psychical Research, as well as a champion of alternative approaches to healing. He challenged his professional colleagues not to let a narrow mindset prevent an honest appraisal of those beliefs.
In an empirical study by Haggbloom et al. using six criteria such as citations and recognition, James was found to be the 14th most eminent psychologist of the 20th Century.