Smith was born in Suzhou, China to Methodist missionaries and spent his first 17 years there. He taught at the Universities of Colorado and Denver from 1944–1947, moving to Washington University in St. Louis, Missouri for the next ten years, and then Professor of Philosophy at MIT from 1958–1973. While at MIT he participated in some of the experiments with entheogens that professor Timothy Leary conducted at Harvard University. He then moved to Syracuse University where he was Thomas J. Watson Professor of Religion and Distinguished Adjunct Professor of Philosophy until his retirement in 1983 and current emeritus status. He now lives in the Berkeley, CA area where he is Visiting Professor of Religious Studies at the University of California, Berkeley.
During his career, Smith not only studied, but practiced Vedanta Hinduism, Zen Buddhism (studying under Goto Zuigan), and Sufism for over ten years each. He is a notable autodidact.
As a young man, Smith, of his own volition, after suddenly turning to mysticism, set out to meet with then-famous author Gerald Heard. Heard responded to Smith's letter, invited him to his Trabuco College (later donated as the Ramakrishna Monastery) in Southern California, and then sent him off to meet the legendary Aldous Huxley. So began Smith's experimentation with meditation, and association with the Vedanta Society in Saint Louis under the auspices of Swami Satprakashananda of the Ramakrishna order.
Via the connection with Heard and Huxley, Smith eventually experimented with Timothy Leary and others at the Center for Personality Research, of which Leary was Research Professor. The experience and history of the era are captured somewhat in Smith's book Cleansing the Doors of Perception. In this period, Smith joined in on the Harvard Project as well, an attempt to raise spiritual awareness through entheogenic plants.
He has been a friend of the XIVth Dalai Lama for more than forty years, and met and talked to some of the great figures of the century, from Eleanor Roosevelt to Thomas Merton.
He developed an interest in the Traditionalist School formulated by Rene Guenon and Ananda Coomaraswamy. This interest has become a continuing thread in all his writings.
In 1996, Bill Moyers devoted a 5-part PBS special to Smith's life and work, "The Wisdom of Faith with Huston Smith." Smith has produced three series for public television: "The Religions of Man," "The Search for America," and (with Arthur Compton) "Science and Human Responsibility." His films on Hinduism, Tibetan Buddhism, and Sufism have all won awards at international film festivals.
His latest DVD release is The Roots of Fundamentalism - A Conversation with Huston Smith and Phil Cousineau.