The origins of the United Church of Religious Science can be traced to various points in Holmes’ life, but he had begun speaking in Los Angeles in 1916 and started to draw crowds of thousands. After the first publication of "The Science of Mind" in 1926, interest really began to grow. In 1926, Holmes began speaking each Sunday morning in a theatre in the Ambassador Hotel, and within a year, the theatre was filled to capacity. Holmes initially resisted the urgings of friends to form a corporation and an organization, but in 1927, a Board of Governors was chosen, and they incorporated the non-profit religious and educational organization, The Institute of Religious Science and School of Philosophy, Inc.

A few months later, the Church launched a monthly magazine, "Religious Science." The magazine was created to sustain and build interest for the many aspiring students who wanted to enroll in and attend the Church. In 1929, the magazine changed its appearance and its title to "Science of Mind."

On April 16, 1935, the original organization was reincorporated as The Institute of Religious Science and Philosophy. By 1939, there were 13 chapters in California, and the Institute obtained the right to ordain its own ministers. The organization continued to grow throughout the 1940s, and in 1953, it became, officially, the Church of Religious Science, with all chapters becoming affiliated churches.

Since then, other areas of growth include the establishment of the Science of Mind Foundation in 1986 and the launching of the Holmes Institute in 1997.