Exposed to drawing at an early age through visiting her father’s architectural studio, she enrolled at the Academia de Bellas Artes Hernando Siles in 1936, studying under Cecilio Guzmán de Rojas (1899-1950) and Jorge de la Reza (1901-1958). She also took correspondence courses in art. Joining the newspaper La Razón [The reason] in 1946 as a portraitist and illustrator, she soon rose to be director of the art and literary section. It was not until 1951 that she took to painting as her medium of choice. A recipient of a fellowship from the Spanish government, M. L. Pacheco travelled to Madrid to attend the Real Academia de Bellas Artes de San Fernando. She also frequented the studio of Daniel Vázquez Díaz (1882-1969), a neo-cubist portrait and landscape artist interested in planes, colour and light, who, along with Pablo Picasso (1881-1973), would profoundly influence her art. Returning to La Paz in April 1952, she taught at the Escuela de Bellas Artes, soon becoming part of the avant-garde as a founder of the collective Los Ocho Contemporáneos, whose members dominated the mid-century Bolivian abstract art scene. After securing first prize at the Salón Nacional Pedro Domingo Murillo in 1953  and a special prize at the II Bienal Hispanoamericana in Havanain 1954, M. L. Pacheco’s career ascended while her marriage faltered. In 1956, at the age of 37, María Luisa Pacheco left the comforts of an upper-middle-class existence in her hometown of La Paz, Bolivia, to pursue a professional painting career in New York.

It was in New York, however, that M. L. Pacheco’s style fully emerged. Receiving three consecutive Guggenheim Fellowships (1958-1960), she maintained a studio practice that allowed her unrestricted experimentation. Moving away from the semi-figurative abstraction that had characterised her early period, she enthusiastically embraced a new aesthetic vocabulary of art informel and abstract expressionism. Dominated by monumental vertical elements devoid of any referents, her austere compositions evidence her conscious attention to detail as seen in the artwork Inca of 1964. Juxtaposed planes, angles, lines, textures – generated by the incorporation of sand, wood, newspaper, and fabric on the canvas – and gestural strokes were carefully arranged on an underlying geometric grid as evidenced in Ritual of 1967. Her work was included in the 1959 São Paulo Biennial where she received an award, and shown in the exhibitions South American Art Today at the Dallas Museum of Art in the same year, New Departures: Latin America at the Institute of Contemporary Art in Boston in 1960, and Magnet New York: A Selection of Paintings by Latin American Artists Living in New York at Galeria Bonino in New York in 1964. At this same time, she also worked as a textile designer for the leading fabric houses in New York.

M. L. Pacheco achieved her mature style in the 1970s. Returning to aspects of the human shape, she synthesised the planes in large-format compositions to depict chains of overlapped nature-like volumes. Represented by the prestigious Lee Ault & Company, she became an established contemporary artist. M. L. Pacheco died in New York in 1982. In 1986, during the celebration of its tenth anniversary, the Museum of the Modern Art of Latin America (now the Art Museum of the Americas) in Washington DC organised a retrospective tribute to the artist. She is one of the most significant artists in the history of the modern art of the Americas.