Hay recounted her life story in an interview with Mark Oppenheimer of the New York Times in May 2008. In it Hay stated that she was born in Los Angeles to a poor mother who remarried Louise’s violent stepfather. She recounted that when she was about 5, she was raped by a neighbor. At 15 she told how she dropped out of high school without a diploma, became pregnant and, on her 16th birthday, gave up her newborn baby girl to be adopted. She then recalled she moved to Chicago, where she worked in low paying jobs. In 1950 she moved on again to New York. At this point, she explained , she changed her name and began a career as a fashion model. She was successful at this, working for Bill Blass, Oleg Cassini and Pauline Trigère. In 1954 she married the English businessman Andrew Hay, but went on to tell how, after 14 years of marriage, she was devastated when he left her for another woman.

Hay said that about this time she found the First Church of Religious Science on 48th Street, that taught her the transformative power of thought. Hay revealed that here she studied the metaphysical works of authors like Florence Scovel Shinn, who claimed that positive thinking could change people’s material circumstances, and the Religious Science founder Ernest Holmes, who taught that the body could be healed through positive thinking .

By Hay's account in the early 1970s she became a Religious Science practitioner. In this role she led people in spoken affirmations, which she believes will cure their illnesses, and became popular as a workshop leader. She also recalled how she had studied Transcendental Meditation with the Maharishi Mahesh Yogi at the Maharishi International University in Fairfield, Iowa.

Hay described how in 1977 or 1978 she found she had cervical cancer, and how she came to the conclusion that by holding on to her resentment for her childhood abuse and rape she had contributed to its onset. She reported how she had refused conventional medical treatment, and began a regime of forgiveness, coupled with therapy, nutrition, reflexology and occasional enemas. She claimed in the interview that she rid herself of the cancer by this method, but declared that there is no doctor left alive who can confirm this story , while swearing to its truth.

In 1976, Hay wrote her first book Heal Your Body , this began as a small pamphlet, containing a list of different bodily ailments and their “probable” metaphysical causes. This pamphlet was later enlarged and extended into her book You Can Heal Your Life , published in 1984 As of February 2008, it is still on New York Times best sellers list.

Around the same time she began leading support groups for people living with H.I.V. or AIDS which she called "Hay Rides". These grew from a few people in her living room to hundreds of men in a large hall in West Hollywood. Her work with AIDS patients drew fame and she was invited to appear on “The Oprah Winfrey Show” and “Donahue” in the same week, in March 1988. Following this You Can Heal Your Life immediately landed on the New York Times best-seller list. More than 35 million copies are now in print around the world in over 30 languages. and has been made into a movie. You Can Heal Your Life is also included in the book 50 Self-Help Classics for being significant in its field.

In 1984, Louise Hay established Hay House Publishing, which is the primary publisher of books and audio books by Deepak Chopra and Doreen Virtue, as well as many books by Wayne Dyer. In addition to running her publishing company, Hay runs a charitable organization called 'Hay Foundation', which she founded in 1985.

In 2008, a movie about Louise Hay's life was released, titled You Can Heal Your Life. In Louise's own words from the movie's official website: "This movie is the story of my life, my teachings, and how I've applied the principles of my teachings to my own life." The movie also features Gregg Braden, Wayne Dyer, Gay Hendricks, Esther & Jerry Hicks, Doreen Virtue, and was directed by Emmy Award winning Director Michael Goorjian

According to P. Randall Cohan, the "timeless message" of Louise Hay's You Can Heal Your Life "is that we are each responsible for our own reality and "dis-ease".