She grew up in a wealthy Jewish family in Manhattan, New York City and attended Franklin School (now Dwight School) and Quintano’s School for Young Professionals, graduating from the latter in 1968. At about that time, she began writing about the music scene for a small Greenwich Village newspaper. She met Keith Emerson, then member of the rock band The Nice and later of Emerson, Lake & Palmer, and they were briefly engaged. According to Odzer, Emerson broke off the engagement when he saw a Time Magazine article that published her photo and described her as a "Super Groupie." Thereafter she recorded an album called The Groupies, produced by Alan Lorber, which was essentially a 1969 recording of interviews with Cleo and some friends describing their adventures meeting (and sleeping with) rock musicians.

In the early 1970s, Odzer traveled in Europe and the Middle East and worked as a model. She spent the late 1970s in the hippie culture of Anjuna, Goa in India. Her experiences there, including heavy use of cocaine and heroin, the international drug smuggling used to finance the stay, and her subsequent two-week incarceration, would later form the basis of her second book, Goa Freaks: My Hippie Years in India. (1995, ISBN 156201059X) For a time she followed the teachings of Bhagwan Shree Rajneesh in India. Ma Prem Madhumaya

After her return to the United States in 1980, Odzer underwent drug treatment. She entered college, then graduate school, and eventually obtained a Ph.D. in anthropology from The New School for Social Research in New York City with a thesis on prostitution in Thailand. Beginning in 1987, she had spent three years in Thailand to research this topic. In her dissertation, she describes case studies of 17 people connected to the sex industry in Patpong. She concludes that the economic opportunities provided by sex work do not translate into a higher status of women, because of persistent stigma and ideas about gender inequality in Thai society. Her experiences in Thailand were described in her first book, Patpong Sisters: An American Woman's View of the Bangkok Sex World (1994, ISBN 1559702818) In this work she describes the Thai prostitutes she got to know as quick-witted entrepreneurs rather than exploited victims, sometimes revered in their poor home villages. She also relates her own problematic affair with a Thai pimp boyfriend.

Following publication of the book, Odzer worked at Daytop in New York, a drug rehabilitation organization.

From 1995 to 1998, Odzer produced several dozen episodes of her show Cleo's Adventures for Manhattan Neighborhood Network public-access TV. Her third book, Virtual Spaces: sex and the cyber citizen (1997, ISBN 0425159868) deals with cybersex. She appeared in episode 1.21 of SexTV in 1999, with a segment on cybersex.

Disappointed with life in New York, in 1999 Odzer returned to Goa, where some of the remaining old-time hippies disliked her because of the publicty her book had brought to the scene. She died there in 2001. A search of the Internet reveals various purported causes of death including brain tumor, stroke, brain hemorrhage, AIDS, drug overdose, and "female internal organ problems". A good friend of hers who had been corresponding with Odzer during her final stay in India, "Cookie" (with whom she recorded The Groupies), reports that Odzer's doctor (who had been away when she died) said she probably died of a stroke related to very high cholesterol and serious circulatory problems that she was being treated for during her final year, and that her body had been cremated after a small service. But a researcher, Arun Saldanha, who interviewed members of the Goa community about Odzer, reports being told by a psychiatrist at the Goa Medical College some ten months after her death that her body had lain unclaimed in a morgue in Mapusa for more than a month until finally she had been buried in Mapusa without a funeral, and that she had had AIDS. Saldanha also reports having seen Odzer use cocaine during an interview he had with her sometime before her death.

The 2002 documentary Last Hippie Standing covered the Goa scene and featured some of Cleo Odzer's old super-8 footage from the 1970s. She was interviewed for the film in Goa shortly before her death:

I don't know what the future brings, but I know what I don't want: New York is what I don't want, that culture is what I don't want; it's not right. I don't know what is right. I don't think our old life was right. I don't see a new culture that is right, but we have to continue trying, that's the best we can do, that's the best any of us can do, to keep trying. To make something that is peaceful for everybody, that makes people happy, that is fair to everybody. And that's all I want.

The film is dedicated to her memory.