Dyer was born in Detroit, Michigan to Melvin Lyle (deceased) and Hazel Irene Dyer, and spent much of his adolescence in an orphanage on the east side of Detroit. Dr. Wayne Dyer is a 1958 graduate of Denby High School; he received his D.Ed. degree in counseling from Wayne State University. Dyer was a guidance counselor in Detroit at the high school level and a professor of counselor education at St. John's University in New York. He served in the United States Navy from 1958-1962.

He first pursued an academic career, publishing in journals and running a successful private therapy practice, but his lectures at St. John's, which focused on positive thinking and motivational speaking techniques, attracted students beyond those enrolled. A literary agent persuaded Dyer to package his ideas in book form, resulting in Your Erroneous Zones; although initial sales were thin, Dyer quit his teaching job and began a publicity tour of the United States of America, doggedly pursuing bookstore appearances and media interviews ("out of the back of his station wagon", according to Michael Korda, making the best-seller lists "before book publishers even noticed what was happening"), which eventually led to national television talk shows including Merv Griffin, The Tonight Show, and Phil Donahue.

Dyer proceeded to build on his success with lecture tours, a series of audiotapes, and regular publication of new books. Dyer's audience was not limited to business as with Dale Carnegie or Stephen Covey, and so his message resonated with many in the New Thought Movement and beyond. He often recounted anecdotes from his family life, and repeatedly used his own life experience as an example. His self-made man success story was a part of his appeal. Dyer told readers to pursue self actualization, calling reliance on the self as a guide to "religious" experience, and suggested that readers emulate Jesus Christ, whom he termed both an example of a self-actualized person, and a "preacher of self-reliance". Dyer criticized societal focus on guilt, which he saw as an unhealthy immobilization in the present due to actions taken in the past. He advocated readers to see how parents, institutions, and even they, themselves, have imposed guilt trips upon themselves.

Although Dyer resisted the spiritual tag, by the 1990s he was altering his message to include more components of spirituality, in Real Magic, and higher consciousness, in Your Sacred Self. Currently, his focus is on interpretations of Tao Te Ching and he has many U.S. speaking engagements.

Dyer lives in Maui, Hawaii. He has been married three times, having seven of his eight children by his third wife, Marcelene. Wayne and Marcelene Dyer's children are Shane, Stephanie, Skye, Sommer, Serena, Sands and Saje. His oldest daughter, from his first marriage to a woman name Judy, is named Tracy. All of his children live in Florida.

In 2009 Dyer announced that he has chronic lymphocytic leukemia.

"My belief is that the truth is a truth until you organize it, and then becomes a lie. I don't think that Jesus was teaching Christianity, Jesus was teaching kindness, love, concern, and peace. What I tell people is don't be Christian, be Christ-like. Don't be Buddhist, be Buddha-like."

"Religion is orthodoxy, rules and historical scriptures maintained by people over long periods of time. Generally people are raised to obey the customs and practices of that religion without question. These are customs and expectations from outside the person and do not fit my definition of spiritual."

Since 2000, he has appeared many times on PBS during their pledge drives. Although PBS' local station managers believe that he is a popular speaker and successful in helping their stations raise money, some PBS viewers found the appearances disturbing in the sense "that PBS might be seen as lending its prestige to Dyer's spiritual views and aligning itself with his teachings". Other criticisms included skepticism of his status as a "spiritual mentor" and characterizing his teachings as consisting of superficial platitudes. Viewers also expressed displeasure at the idea that Dyer himself must be profiting financially from this exposure of teachings they considered non-rigorous and lacking practical or intellectual value.

On May 24, 2010, author Stephen Mitchell sued Dyer for plagiarism, accusing him of taking 200 lines of his interpretation of the Tao Te Ching for Dyer's books Living the Wisdom of the Tao and Change Your Thoughts -- Change Your Life.