In 1923, Stone received his bachelor's degree from the University of California, Berkeley. In the 1960s, Stone received an honorary Doctorate of Letters from the University of Southern California, where he had previously earned a Masters Degree from the College of Letters, Arts, and Sciences.

When at home, Stone relied upon the research facilities and expertise made available to him by Esther Euler, head research librarian of the University of California at Los Angeles, to whom he dedicated and thanked, in addition to many others, in several of his works.

Stone enjoyed a long marriage to his wife and editor on many of his works, Jean Stone. The Stones lived primarily in Los Angeles, California. During their lifetime, Stone and his wife funded a foundation to support charitable causes they believed in.

Stone's main source for Lust for Life, as noted in the afterword, were Van Gogh's letters to his brother Theo. Stone additionally did much of his research "in the field". For example, he spent many years living in Italy while working on The Agony and the Ecstasy. The Italian government lauded Stone with several honorary awards during this period for his cultural achievements highlighting Italian history.

Stone wrote at length about the life and work of Charles Darwin in his bookThe Origin, after doing meticulous research. How Darwin's accidental five year voyage on The Beagle led to his extensive observations and writings. Eventually leading to his theory of evolution, which shook the contemporary conservative British society to its core.

Stone wrote in great detail about Sigmund Freud's life and his contributions to the field of psychoanalysis in his book The Passions of the Mind. His background as a medical researcher in Vienna, his study in Paris with Dr. Charcot and translation of his works into German, how his thinking leads him to the concept of unconscious. These coupled with his ideas of the linkage between sex and unconscious, creates ripples in the conservative Vinnese psychiatry circles. Slowly a band of followers emerge, notable ones being Carl Jung, Karl Abraham etc. Some of them defect later to come up with some dissenting views. On the personal side, Sigmund's happy married life with his lady love Martha Bernays. Against the brewing anti-semitic atmosphere in Vienna just prior to beginning of world war 2, Sigmund moves to London for the final years of his life.

In 1953, a popular film version was made of The President's Lady based on his 1950 novel of the same name, starring Charlton Heston as Andrew Jackson and Susan Hayward as Rachel Donelson Jackson. In 1956, a film version was made of Lust for Life, based on his 1934 novel, starring Kirk Douglas as Van Gogh. In 1965, a film was made of The Agony and the Ecstasy, starring Heston as Michelangelo and Rex Harrison as Pope Julius II.

Some of Stone's important historical biographical works include:

• Lust for Life (1934) - based on the life of Vincent van Gogh
• Sailor on Horseback (1938) - based on the life of Jack London.
• Clarence Darrow For the Defense (1941) - biography of Clarence Darrow
• They Also Ran (1944, updated 1966) - based on candidates who were defeated for U.S. President
• Immortal Wife (1944) - based on the life of Jessie Benton Frémont
• Adversary in the House (1947) - based on the life of Eugene V. Debs and his wife Kate, who opposed socialism
• Earl Warren (1948) - biography of Earl Warren
• The Passionate Journey (1949) - based on the life of American artist John Noble
• Love is Eternal (1954) - based on the marriage of Abraham Lincoln and Mary Todd
• Men to Match My Mountains (1956) - based on the opening of the Far West, 1840 - 1900
• The Agony and the Ecstasy - (1961) - based on the life of Michelangelo
• Those Who Love (1965) - based on the life of John Adams and Abigail Adams
• The Passions of the Mind (1971) - based on the life of Sigmund Freud
• The Greek Treasure (1975) - based on the discovery of Troy by Heinrich Schliemann
• The Origin (1980) - based on the life of Charles Darwin
• Depths of Glory (1985) - based on the life of Camille Pissarro