While living in Chile during the mid-1960s, Vicuña began an ongoing series of small sculptures she calls precarios, spatial poems in which she combines feathers, stone, plastic, wood, wire, shells, cloth, and other human-made detritus. These tiny sculptures are often loosely fastened together with string, so the materials appear to have gathered naturally. These works are defined by their fragility and ephemerality: Vicuña initially composed the precarios along the ocean's edge, so that they would inevitably be erased by the high tide. Around the same time, Vicuña became interested in ancient quipus—an Incan method of visual communication and record-keeping involving the knotting of colored strings. Her first spatial weavings date from the early seventies, and soon after she began to make her own Quipus from unspun wool—ephemeral, site-specific installations which combined the tactile ritual of weaving and spinning with assemblage, poetry, and performance. Vicuña's surreal figurative paintings of the 1970s are more explicitly personal and political than her other bodies of work, and were in direct response to the unrest in Chile and her subsequent exile. These paintings refer to the subtly subversive images made by 16th-century indigenous artists in Latin America after the Spanish conquest, when they were forced to paint angels and saints for the Catholic church. In Vicuña's paintings, religious icons are replaced by personal, political, and literary figures, commemorated and mythologized by the artist.

Vicuña received her MFA from the National School of Fine Arts, University of Chile in 1971 and continued with postgraduate studies at Slade School of Fine Art, University College London from 1972-1973. Solo exhibitions of her work have been organized at Contemporary Arts Center, New Orleans, LA, 2017; Museo de la Memoria y los Derechos Humanos, Santiago, Chile, 2014; Museo Nacional de Bellas Artes, Santiago, Chile, 2014; FRAC Lorraine, Metz, France, 2013; Institute for Women and Art, Rutgers University, New Brunswick, NJ, 2009; The Drawing Center, New York, 2002; and the Boulder Museum of Contemporary Art, Boulder, CO, 2002. Group exhibitions and biennials featuring her work include Documenta 14, Athens, Greece and Kassel, Germany (2017); Radical Women: Latin American Art 1960-1985, Hammer Museum, Los Angeles, 2017; 18th Sydney Biennale, Australia (2012); DANCE / DRAW, the Institute of Contemporary Art, Boston, 2011; ONLIN__E, Drawing Through the Twentieth Century, Museum of Modern Art, New York, 2010; WACK! Art and the Feminist Revolution, the Museum of Contemporary Art, Los Angeles, 2007; BIENNIAL Exhibition at the Whitney Museum of American Art, New York, 1997; and INside the VISIBLE curated by Catherine M. de Zegher, Institute of Contemporary Art, Boston, traveled to the National Museum of Women in the Arts, Washington, DC, the Whitechapel Art Gallery, London, and the Art Gallery of Western Australia, Perth, 1996. Her work is in numerous international private and public collections, including Tate Gallery, London; FRAC Lorraine, Metz, France; Museo de Arte Contemporáneo, Santiago, Chile; Museo Nacional de Bellas Artes, Santiago, Chile; UC Berkeley Art Museum, Berkeley, CA; and the Blanton Museum of Art at The University of Texas at Austin, TX.

Vicuña is the author of 20 volumes of art and poetry published in the U.S., Europe, and Latin America. Her filmography includes documentaries, animation, and visual poems. Vicuña has received several awards, including The Anonymous Was a Woman Award, New York (1999); and The Andy Warhol Foundation Award (1997), and in 2015 was appointed the messenger lecturer at Cornell University.