After graduating in 1963 from Wakefield High School, Adams completed pre-med coursework at George Washington University. He began medical school without an undergraduate degree, and earned his Doctor of Medicine degree at Virginia Commonwealth University (Medical College of Virginia) in 1971. In the late 1960s one of his closest friends (a man, not a woman as depicted in the Patch Adams film) was murdered. Convinced of the powerful connection between environment and wellness, he believes the health of an individual cannot be separated from the health of the family, community, and the world. While working in an adolescent clinic at MCV, in his final year of med school, he met Linda Edquist, a fellow VCU student who volunteered in the clinic.

Soon after graduation, Patch, Linda, and friends founded the Gesundheit! Institute (originally known to many as the Zanies), which ran as a free community hospital from 1971 to 1983.

Adams and Edquist married in 1975 and had two sons, Atomic Zagnut "Zag" Adams and Lars Zig Edquist Adams; they divorced in 1998.

Since the 1990s Adams has supported the Ithaca Health Alliance (IHA), founded as the Ithaca Health Fund (IHF) by Paul Glover. In January 2006 IHA launched the Ithaca Free Clinic, bringing to life key aspects of Adams' vision. Adams has also given strong praise to Health Democracy, Glover's book written and published the same year.

Adams was awarded the Peace Abbey Courage of Conscience Award on January 29, 1997.

The 1998 film Patch Adams was based on Adams' life and views on Medicine. Adams has heavily criticized the film, saying it eschewed an accurate representation of his beliefs in favor of commercial viability. He said that out of all aspects of his life and activism, the film portrayed him merely as a funny Doctor. Patch Adams also said of Robin Williams in an interview, "He made $21 million for four months of pretending to be me, in a very simplistic version, and did not give $10 to my free hospital. Patch Adams, the person, would have, if I had Robin's money, given all $21 million to a free hospital in a country where 80 million cannot get care."

The 2003 Bollywood film Munna Bhai M.B.B.S. was inspired by the movie 'Patch Adams' based on Hunter Doherty's life and his unconventional methods of treating patients. The film brought his methods to the forefront in India and Pakistan where conventional methods were predominant.

In October 2007, Adams and the Gesundheit Board unveiled its campaign to raise $1 million towards building a Teaching Center and Clinic on its land in West Virginia. The Center and Clinic will enable Gesundheit to see patients and teach health care design.

In 2008, Adams agreed to become honorary chair of the "International Association for the Advancement of Creative Maladjustment" or IAACM. In a number of his speeches and essays, Martin Luther King, Jr., had called for such an IAACM, but none was ever created. MindFreedom International, a nonprofit coalition that Gesundheit! belongs to as a sponsor group, launched the IAACM to support "creative maladjustment" and social change.