Graham was born in 1794 in Suffield, Connecticut, to a family with 17 children; his father was 70 years old when Graham was born and his mother was mentally ill. His father died when Graham was two, and he spent his childhood moving from one relative’s home to another. One of his relatives ran a tavern where Graham was put to work; his experience with drunkenness there led him to hate alcohol his whole life and forswear drinking, which made him an exception among his peers at the time. He was often sick, and missed a great deal of schooling. He worked as a farm hand, cleaner, and teacher before deciding on the ministry as an antidote for his poor health. He entered preparatory school at Amherst Academy in his late 20s to become a minister, as his father and grandfather had been. Here, his gift for oratory was recognized. He was expelled from the academy when his schoolmates claimed he had improperly approached a woman.

The Philadelphia Temperance Society was led not by ministers, as most other temperance societies were, but by doctors who were primarily concerned with the health effects of consuming alcohol. Moving in that company, Graham may have met two of the other fathers of American vegetarianism: William Metcalfe, an English minister who established a vegetarian church in Philadelphia, and William A. Alcott, a Philadelphia doctor who wrote extensively about vegetarianism and wrote the first American vegetarian cookbook. Graham taught himself about physiology and apparently arrived at his own conclusion that meat was just as much an expression of and spur to gluttony as alcohol was, that they corrupted both the body and soul of individuals and harmed families and society. His belief was influenced by the book Treatise on Physiology by François-Joseph-Victor Broussais, published in Philadelphia in 1826, that claimed what people ate had enormous influence on their health. Graham’s interest was also captured by the books written by the German chemist, Friedrich Accum, called Treatise on Adulteration of Foods, and Culinary Poisons, in which he denounced the use of chemical additives in food and especially in bread, and Treatise on the Art of Making Good and Wholesome Bread. Wheat flour at that time was often doctored to hide odors from spoilage, to extend it, and to whiten it, and bread was made from very finely ground flour (which Graham viewed as “tortured”) and brewers yeast (used to make beer).

The expulsion caused Graham a nervous breakdown. To recover, he moved to Little Compton, Rhode Island. There, he met and married Sarah Earle, who had nursed him back to health. He studied theology privately, and in 1828 began working as an itinerant preacher at the Bound Brook Presbyterian Church in Bound Brook, New Jersey.

In 1830, Graham accepted a position at the Philadelphia Temperance Society. He left six months later to focus on preaching health.

As a skilled and fiery preacher, his peculiar message, combining patriotism, theology, diet, lifestyle, and messages already prevalent from the temperance movement, captured the attention of the frightened public and outraged bakers and butchers, as well as the medical establishment. When the cholera epidemic reached New York in 1832, people who had followed his advice appeared to thrive, and his fame exploded. When he published his first book in 1837, Treatise on Bread and Bread-Making, his lectures in New York and Boston that year were thronged; the Boston lecture was disrupted by a threat of riots by butchers and commercial bakers.

From these views, Graham created a theology and diet aimed at keeping individuals, families, and society pure and healthy – drinking pure water and eating a vegetarian diet anchored by bread made at home from flour coarsely ground at home so that it remained wholesome and natural, containing no added spices or other “stimulants” and a rigorous lifestyle that included sleeping on hard beds and avoiding warm baths. The regimen has been described as an early example of preventive medicine. The emphasis on milling and baking at home was part of his vision of America in which women remained at home and nursed their families into health and maintained them there, as his wife had done for him. Graham believed that adhering to such diet would prevent people from having impure thoughts and in turn would stop masturbation (thought by Graham to be a catalyst for blindness and early death) His piece On Self-Pollution, published in 1834, contributed to the masturbation scare in antebellum America. He believed youthful masturbation was dangerous to children’s health because of the immaturity of their reproductive organs.

In 1837, Colonel John Benson, Graham and William Alcott founded the American Physiological Society (APS) in Boston to promote Grahamism. Alcott was first President of the Society. After a year, the Society was reported to have had 251 members, including 93 women. It lasted just three years.

In 1837, Graham and David Cambell founded The Graham Journal of Health and Longevity. It was “designed to illustrate by facts, and sustain by reason and principles the science of human life as taught by Sylvester Graham”. It was edited by Campbell, Secretary of the APR (1837–1839) and five volumes were published. In 1840, the journal merged with the Library of Health, edited by Alcott.

In 1850, Alcott, William Metcalfe, Russell Trall, and Graham founded the American Vegetarian Society in New York City, modeled on a similar organization established in Great Britain in 1847.