Guillermoprieto was born and grew up in Mexico City. In her teens, she moved to New York City with her mother where she studied modern dance for several years. From 1962 until 1973, she was a professional dancer.

Her first book, Samba (1990), was an account of a season studying at a samba school in Rio de Janeiro.

In the mid-1970s, she started her career as a journalist for The Guardian, moving later to the Washington Post. In January, 1982, Guillermoprieto, then based in Mexico City, was one of two journalists (the other was Raymond Bonner of The New York Times) who broke the story of the El Mozote massacre in which some 900 villagers at El Mozote, El Salvador, were slaughtered by the Salvadoran army in December, 1981. With great hardship and at great personal risk, she was smuggled by FMLN rebels to visit the site approximately a month after the massacre took place. When the story broke simultaneously in the Post and Times on January 27, 1982, it was dismissed as propaganda by the Reagan administration. Subsequently, however, the details of the massacre as first reported by Guillermoprieto and Bonner were verified, with widespread repercussions.

During much of the subsequent decade, Guillermoprieto was a South America bureau chief for Newsweek.

Guillermoprieto won an Alicia Patterson Journalism Fellowship in 1985 to research and write about changes in rural life under the policies of the European Economic Community.

During the 1990s, she came into her own as a freelance writer, producing long, extensively researched articles on Latin American culture and politics for The New Yorker, and The New York Review of Books, including outstanding pieces on the Colombian civil war, the Shining Path during the Internal conflict in Peru, the aftermath of the "Dirty War" in Argentina, and post-Sandinista Nicaragua. These were bundled in the book 'The Heart That Bleeds' (1994), now considered a classic portrait of the politics and culture of Latin America during the "lost decade" (it was published in Spanish as 'Al pie de un volcán te escribo — Crónicas latinoamericanas' in 1995).

In April 1995, at the request of Gabriel García Márquez, Guillermoprieto taught the inaugural workshop at the Fundación para un Nuevo Periodismo Iberoamericano, an institute for promoting journalism that was established by García Márquez in Cartagena de Indias, Colombia. She has since held seven workshops for young journalists throughout the continent.
That same year, Guillermoprieto also received a MacArthur Fellowship.

A second anthology of articles, 'Looking for History', was published in 2001, which won a George Polk Award. She also published a collection of articles in Spanish on the Mexican crisis, El año en que no fuimos felices.

In 2004, Guillermoprieto published a memoir, 'Dancing with Cuba', which revolved on the year she spent living in Cuba in her early twenties. An excerpt of it was published in 2003 in The New Yorker. In the fall of 2008, she joined the faculty of the Center for Latin American Studies at the University of Chicago, as a Tinker Visiting Professor.