Barnard grew up in Fargo, North Dakota in a family of cattle ranchers and physicians. He received his M.D. from George Washington University School of Medicine in Washington, D.C.

Barnard trained as a psychiatrist and is board certified by the American Board of Psychiatry and Neurology. For ten years he provided psychiatric services for the Calvary Shelter for Homeless Women in Washington, but then shifted his focus to research the impact of diet on human health, and towards finding alternatives to the use of animals in medical education, testing, and research. Barnard has published his research in academic journals including Lancet Oncology and the American Journal of Cardiology, and is an invited peer reviewer for the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health.

In 2000, in a study conducted with Georgetown University, he demonstrated the role of diet in menstrual disorders, and later conducted studies on diet, weight loss, and insulin sensitivity. In 2002 he published a study showing that oral estrogens are still widely used to suppress growth in adolescent girls.

In 2003, he was awarded a US$350,000 research grant from the National Institutes of Health to study the effect of a low-fat vegan diet on diabetes. The study results, published in Diabetes Care, found that "both a low-fat vegan diet and a diet based on American Diabetes Association guidelines improved glycemic and lipid control in type 2 diabetic patients," but "these improvements were greater with a low-fat, vegan diet" With colleagues at PCRM, he developed an insulin ELISA assay that utilizes monoclonal antibodies from hybridomas maintained in media free of animal products. The test proved as effective as methods that use animal products, and is now produced commercially by Millipore.

In 2004 he formed The Washington Center For Clinical Research, a nonprofit subsidiary of the Physicians Committee for Responsible Medicine that aims to conduct research into the role of nutrition in health. He is now an adjunct associate professor of medicine at GWU and is also a life member of the American Medical Association.

Barnard has written more than a dozen books about nutrition that have, collectively, sold over two million copies. These include The Power of Your Plate (1990), Food for Life (1993), Eat Right, Live Longer (1995), Foods That Fight Pain (1998), and Dr. Neal Barnard's Program for Reversing Diabetes (2007). He is also the editor-in-chief of the Nutrition Guide for Clinicians (2007).

Nutritionist Marion Nestle, while disagreeing with Barnard's vegan principles, noted he raises "provocative questions that deserve serious attention." Dean Ornish has called Barnard "one of the leading pioneers in educating the public about the healing power of diet and nutrition" and Henry Heimlich described his "tremendous influence on dietary practices in the United States." Salon.com praised his ability to promote a vegan diet "with such eloquence as to make the proposition sound almost inviting."

Barnard's nutritional advice is described by Nature Medicine as "not exactly medical gospel," citing as an example his labeling of chocolate, sugar, meat and cheese as "addictive substances" in Breaking the Food Seduction, but the journal also reports that he has "fans high in the medical ranks."

In 1985, Barnard founded the Physicians Committee for Responsible Medicine (PCRM). The organization is opposed to some medical and scientific practices which it considers to be harmful to human health, and promotes the health benefits of a vegetarian diet. PCRM is based in Washington D.C., where a staff of seventy operate within a $7.2 million budget.

With PCRM, Barnard has successfully campaigned against live-animal teaching labs for medical students, something he refused to take part in himself when he was studying medicine. According to Salon.com, by 2001 over half of U.S. medical schools had stopped using live animals for teaching purposes, and by 2006, 85% of schools had abandoned the practice. Barnard also opposes the use of animals in biomedical research and promotes the use of alternatives.

In 1991, he founded The Cancer Project, originally as a PCRM program. It became independently incorporated organization in 2004, with Barnard as president, aiming to educate the public on diet’s role in cancer prevention and survival by providing nutrition and cooking classes for cancer sufferers throughout the U.S.

As president of PCRM, Barnard has been at the forefront of criticism of the high-fat Atkins diet. He runs a website advising of potential health consequences, and warning of the possibility of legal liability for doctors who prescribe the diet. In 2004, he approved the release by PCRM of a medical report on the death Robert Atkins. The New York City medical examiner's office said the report had been "inappropriately obtained" by a cardiologist, who claimed to have provided it to PCRM "for research purposes only." Barnard said the cardiologist was aware the report would be released and justified it to expose the effect of the diet on Atkins' health.

Relationship to various animal rights groups

Until 2005 Barnard sat on the board of the Foundation to Support Animal Protection (which has since become known as The PETA Foundation after it became the legal entity that manages People for the Ethical Treatment of Animals' assets). Collectively PETA and the Foundation have given more than $1.3m to PCRM. Barnard also writes a column, called "Doctor in the House", for Animal Times, PETA's quarterly magazine. Some organizations - the Center for Consumer Freedom, the American Council on Science and Health and Foundation for Biomedical Research - have accused PCRM of being a front organization for People for the Ethical Treatment of Animals (PETA) activism. In a 2004 article about connections between animal rights groups, The Observer described PCRM as a "quasi-scientific organisation part-funded by PETA."

In a 2005 response to what PCRM called "attacks" by the food and tobacco industry, the group acknowledged PETA's support "in years past" but affirmed itself as an "entirely independent organization." In 2006 Barnard told The Columbus Dispatch there are no current links between PCRM and PETA, though noted "I like the work they do, and I hope they keep doing it".

In an article examining the relationships between animal rights organizations in the U.S. and U.K., The Observer criticized Barnard in 2004 for having co-signed a letter with Kevin Jonas of Stop Huntingdon Animal Cruelty ... a campaign that has seen several of its leading members, including Jonas, jailed in connection with their activism. PCRM responded that he co-signed "a polite and informative letter" many years before the incident that saw Jonas jailed, and that he had no further interaction with SHAC.

Barnard is also a musician (he plays the electric guitar and keyboards, and sings) and has released several recordings, including a CD with American and Vietnamese musicians, called Verdun (2004). Verdun Previously, he played in the fusion jazz group Pop Maru, Pop Maru - BandToBand.com and also played with the jazz group Quartet. Verdun On May 4, 2009, Barnard’s composition, “Dream of the Black Horse,” was played on the National Mall in Washington, DC, at the conclusion of the Library of Congress’ Journey to Freedom weekend events commemorating the struggles of the Vietnamese boat people after the fall of Saigon.