Her sculptures combine cast bronze or aluminium with braided and twisted silk and wool fibres. The contrast between rigid metal and soft textile became her signature, drawing on her academic training and her study of Benin bronze casting and Senufo textile arts. Confessions for Myself (1972), ten feet tall, is held at the University of California Berkeley. Her Malcolm X Steles, a series begun around 1969, met with a hostile review from New York Times critic Hilton Kramer; art historian Henri Ghent responded that Kramer's real objection was to the works' dignified memorialisation of the civil rights leader. In 1998, her bronze Africa Rising, eighteen feet tall, was installed in New York's Ted Weiss Federal Building, which had been built unknowingly atop an 18th-century African burial ground.

Her literary career runs in parallel. Her 1979 novel Sally Hemings sold over a million hardcover copies, won the Janet Heidinger Kafka Prize, and was dismissed by mainstream historians who denied the Jefferson-Hemings relationship. The 1998 DNA study proved her right. She later settled a ten-million-dollar claim against DreamWorks over plagiarism of her novel Echo of Lions in the film Amistad.

Based in Paris for much of her adult life, Chase-Riboud received France's Legion d'Honneur in 2022. In 2024-25, a retrospective of her work was presented across eight Paris institutions, reportedly the first such honour given to any living artist.