Reggio was born in New Orleans, Louisiana to an old and distinguished Louisiana family descended from Francesco M. de Reggio, an Italian nobleman who first settled in France and then in French Louisiana around 1750.

Reggio co-founded La Clinica de la Gente, a facility that provided medical care to 12,000 community members in Santa Fe, and La Gente, a community-organizing project in northern New Mexico's barrios. In 1963 he co-founded Young Citizens for Action, a community organization project that aided juveniles in the street gangs of Santa Fe. In 1972, he co-founded the Institute for Regional Education in Santa Fe, a non-profit foundation focused on media development, the arts, community organization, and research.

Reggio is most known for his Qatsi trilogy, which includes the films Koyaanisqatsi, Powaqqatsi, and Naqoyqatsi. All of the film titles are taken from the Hopi language; Koyaanisqatsi meaning "life out of balance," Powaqqatsi meaning "life in transformation," and Naqoyqatsi meaning "life as war". In 1995 he directed the short feature entitled Evidence that featured, like the Qatsi Trilogy, a Soundtrack composed by his friend Philip Glass. Also, he has directed a documentary Anima Mundi. This film was funded by the World Wide Fund for Nature to promote their diversity program. Reggio spent fourteen years in fasting, times of silence, and prayer, training to be a monk within the Congregation of Christian Brothers, a Roman Catholic pontifical order, before abandoning that path and making the films.

Reggio has been involved in many progressive political causes in the United States, including work for the American Civil Liberties Union, co-organizing a multi-media public interest campaign on the invasion of privacy and the use of Technology to control behavior. Reggio resides in Santa Fe, New Mexico and focuses on films exploring the negative impacts of consumerism and fundamentalism on the world. Godfrey Reggio participated in the Stock Exchange of Visions project in 2006.

Reggio's most recent film is Visitors, which premiered at the 2013 Toronto International Film Festival. Philip Glass returns as the film's Composer, and Jon Kane as the visual designer (having also worked on Naqoyqatsi with Reggio in 2002).

In 2014 Reggio was recognized by the Museum of Arts and Design in New York City with a full career retrospective entitled Life with Technology: The Cinema of Godfrey Reggio.