He was born in Chicago, Illinois on May 4, 1902. His Father died in 1905 leaving his family in debt. In 1908 he hawked newspapers on the South Side of Chicago while his mother worked as a dressmaker. By 1915 he owned his own newsstand. In 1918 he moved to Detroit to sell casualty insurance for his mother.

In 1919, Stone built the Combined Insurance Company of America, which provided both accident and health insurance coverage; by 1930, he had over 1000 agents selling insurance for him across the United States. By 1979, his insurance company exceeded $1 billion in assets. Combined later merged with the Ryan Insurance Group to form Aon Corporation in 1987., and Combined was later spun off by Aon to ACE Limited in April 2008 for $2.56 billion.

Stone associated with Napoleon Hill to teach the Philosophy of Personal Achievement “Science of Success" course. Stone wrote: "One of the most important days in my life was the day I began to read Think and Grow Rich in 1937. Stone said that the Bible was “the world's greatest self-help book".

Stone emphasized using a "positive mental attitude" to succeed. Stone adopted the motto of his mentor, Napoleon Hill, "Whatever the mind can conceive and believe, the mind can achieve (with PMA)." In 1960, Stone teamed up with Napoleon Hill to author Success Through a Positive Mental Attitude. The book Success Through a Positive Mental Attitude includes the following testimonial from the Rev. Robert H. Schuller on the inside front cover page: "Success Through A Positive Mental Attitude is one of the ten books that has most impacted my faith and my philosophy...no person's education is complete without the concepts articulated in it so wisely and so well." Norman Vincent Peale said that Stone and Hill "have the rare gift of inspiring and helping people...In fact, I owe them both a personal debt of gratitude for the helpful guidance I have received from their writings." Stone and Hill also founded a monthly digest magazine, entitled Success Unlimited. In 1962, Stone wrote the Success System That Never Fails, in which he suggested how to become successful and have a healthy, productive lifestyle. In 1964, he and Norma Lee Browning collaborated on writing The Other Side of the Mind.

Among his philanthropic activities were his long-time support of the Boys Clubs of America (now Boys and Girls Clubs of America), and the National Music Camp at Interlochen, Michigan. The Stone Student Center was dedicated on June 24, 1967 on the campus of the Interlochen Center for the Arts. Stone donated one million dollars to Rev. Dr. Robert H. Schuller to begin construction on the Crystal Cathedral. The W. Clement and Jessie V. Stone Foundation was established by Stone and his wife to support humanitarian, mental health, religious and community causes. In 2009 the Foundation gave $3,805,625 to worthwhile causes. The foundation also gives college scholarships; one of the beneficiaries is the demographer, pollster, and political pundit Elliott Stonecipher of Shreveport, Louisiana, who entered the "Boy of the Year" competition in the late 1960s at the national Boys Clubs competition.

Stone contributed up to $10 million to President Richard Nixon's election campaigns in 1968 and 1972; they were cited in Congressional debates after the Watergate scandal to institute campaign spending limits.

According to Tim Weiner, in One Man Against the World: The Tragedy of Richard Nixon, in 1972 President Nixon’s Lawyer, Herbert Kalmbach, helped raise money for Nixon’s presidential campaign by selling ambassadorships to large donors, including “W. Clement Stone, [who] pledged $3 million." Stone wanted to become ambassador to Great Britain, "which already was occupied by Ambassador Walter Annenberg, who gave $254,000 in order to stay on” (p. 160).

Stone was a living Example of the proverbial rags-to-riches protagonist in the Horatio Alger's stories he loved. Eventually he became an 'angel' to others, lifting some from the gutter to the heights of success. One of his great success stories was Og Mandino, an alcoholic whom Stone took under his wing. The relationship led to a new life for Mandino, who became the publisher of Success Magazine. In 1978, Stone met an aggressive young securities broker named Christopher Nolan and recruited him as his Director of Education for the Entrepreneurship Forums. The forums were created by Stone to educate aspiring Business owners in Chicago.

Stone died on September 3, 2002 in Evanston, Illinois.

Stone was a supporter of The Napoleon Hill Foundation, which he directed for forty years, and to which his estate contributes funding. Stone celebrated his 100th birthday with a gift of $100,000 to the University of Illinois at Chicago.

In the last interview before his death, Stone explained the importance of PMA (Positive Mental Attitude): "A positive mental attitude is necessary for achieving worthwhile success. We in America know what it is for us, for we have inherited the tenets of the Judeo-Christian faiths on which our Constitution, laws and customs have been based.... Strive to understand and apply the Golden Rule.... Believe that any goal that doesn’t violate the laws of God or the rights of your fellow men can be achieved...". Recalled M.L. Harris: "I attended one of the PMA rallies in Minneapolis, Minnesota, in 1976. I'll never forget Stone, the MC of the event; and how he leapt on the stage, grabbed the microphone and shouted: I feel healthy! I feel happy! I feel terrific! It gave me goosebumps. At the time, he was 74 years old; and possessed the Energy of a man in his thirties." ~ M.L. Harris, author.