Working for the American Museum of Natural History, she and her husband Gladwyn Kingsley Noble discovered a new species of frog, the Eleutherodactylus ruthae, named for her.

[4] While at the museum, the Nobles undertook an expedition to Hispaniola to study the rhinoceros iguana and the Hispaniolan giant tree frog, both of which were very poorly known to science at the time.

[3] In 1945,[6] Noble published The Nature of the Beast, a book written on animal behavior based on research and notes by her husband.

[6][10] The manuscript was read by both psychologists and naturalists prior to publication: Robert Yerkes, Frank Beach, and Ernst Mayr were among those given access to portions of it.

[6] Writing in the Annals of the Entomological Society of America, a reviewer stated that the book had the "rare quality of combining entertainment with sound scientific value".