At the age of 17, Helena Hahn married Nikifor V. Blavatsky, a Russian military officer and provincial vice-governor, but they separated after a few months. She became interested in occultism and spiritualism and for many years traveled extensively throughout Asia, Europe, and the United States; she also claimed to have spent several years in India and Tibet studying under Hindu gurus. In 1873 she went to New York City, where she met and became a close companion of Henry Steel Olcott (Olcott, Henry Steel), and in 1875 they and several other prominent persons founded the Theosophical Society.

In 1877 her first major work, Isis Unveiled, was published. In this book she criticized the science and religion of her day and asserted that mystical experience and doctrine were the means to attain true spiritual insight and authority. Although Isis Unveiled attracted attention, the society dwindled. In 1879 Blavatsky and Olcott went to India; three years later they established the Theosophical Society headquarters at Adyar, near Madras, and began publication of the society's journal, The Theosophist, which Blavatsky edited from 1879 to 1888. The society soon developed a strong following in India.

Asserting that she possessed extraordinary psychic powers, Blavatsky, during journeys to Paris and London, was accused by the Indian press late in 1884 of concocting fictitious spiritualist phenomena. After protesting her innocence while on a tour of Germany, she returned to India in 1884 and met with an enthusiastic reception. The “Hodgson Report,” the findings of an investigation in 1885 by the London Society for Psychical Research, declared her a fraud. Soon thereafter she left India in failing health. She lived quietly in Germany, Belgium, and finally in London, working on her small, meditative classic The Voice of Silence (1889) and her most important work, The Secret Doctrine (1888), which was an overview of theosophical teachings. It was followed in 1889 by her Key to Theosophy. Her Collected Writings were published in 16 volumes (1950–91).