She published and promoted her best-known work, Mother India (1927), a deeply critical book on Indian society, religion, and culture.

Written in opposition to the Indian independence movement, the book received a sharply divided reception upon its publication and was accused by several authors of being Indophobic, including Mahatma Gandhi.

[2] Mayo also became a member of the Mayflower Society and maintained links with the Daughters of the American Revolution, which at the time largely shared her hostility towards non-white and Catholic immigration to the United States.

[3][4] Mayo claimed that "negroes" were sexually aggressive and lacked self-control, thus rendering them a threat to "innocent white Anglo-Saxon women".

[5] Written in opposition to the movement for Indian independence, Mayo criticized India's treatment of women, the Dalits, its animals, and the character of its nationalistic politicians.

Mayo's claims were supported by the colonial government as a countermeasure to growing sympathies for the Indian independence movement among outside observers.

[7] It was criticized by Indian independence activist Mohandas Karamchand Gandhi, who wrote in response: This book is cleverly and powerfully written.