The political perspectives of Portillo's films have been described as "nuanced" and versed with a point of view balanced by her experience as a lesbian[1] and Chicana woman.

[4] She had thus been making award-winning films about Latin American, Mexican, and Chicano/a experiences and social justice issues both as a director and screenwriter[5] for about forty years.

By the time she was in Portillo twenties, she had gotten a job working for an educational film company in Los Angeles, exposing her to her future career in documentary filmmaking.

[8] Wanting to work in a more livelier art film community, Portillo decided to move to San Francisco in the early 1970s.

[9] It was followed by The Mothers of Plaza de Mayo, a 1986 co-production with the Argentine director Susana Blaustein Muñoz who she met during her studies at the San Francisco Art Institute.

[10] Portillo's film audience greatly expanded beyond the U.S. and played a major role in publicizing internationally the plight of the mothers and missing children.

According to Portillo, the film was originally supposed to be made alongside Susana Blaustein Muñoz, and together they put in an application to the Corporation for Public Broadcasting to make La Ofrenda.

[9] Portillo humorously mixed political satire and experimental video techniques, putting the figure Columbus in a modern day courtroom and being charged for his atrocities against Native Americans.

The Devil Never Sleeps (1994), one of her most critically acclaimed films, perfectly encapsulates Portillo's experimental filmmaking style as well as her interest and connection to her Mexican roots.

From scenes paired with clips of a TV screen playing Mexican telenovelas, to the recreations of family stories with toy props, The Devil Never Sleeps captures the uniqueness of Portillo's experimental filmmaking style.

After abiding to most of the film edits, the following year, after viewing the final version shortly before the film's broadcast on public television's Point of View, he demanded even more edits to which Portillo refused, agreeing to only one of his demands even after threatening to sue her for libel and even attempting to block the national broadcast.