Beginning in 1908, he collaborated with American composer Charles Wakefield Cadman to develop an opera, Da O Ma (1912), based on his stories of Omaha life, but it was never produced.

Later he attended college and law school in Washington, D.C. By 1853, Iron Eye was a chief of the Omaha; he helped negotiate the 1854 treaty by which the tribe sold most of their land in Nebraska.

Francis' half-siblings became accomplished adults: Susette LaFlesche was an activist and nationally known speaker on issues of Indian rights and reform; Rosalie LaFlesche Farley was an activist and managed Omaha tribal financial affairs; and Susan La Flesche was the first Native American woman trained as a European-American style doctor; she treated the Omaha for years.

Susette "Bright Eyes" La Flesche had been involved as an interpreter for the chief Standing Bear and an expert witness on Indian issues.

In 1881 Susette and the journalist Thomas Tibbles accompanied Alice C. Fletcher, an anthropologist, on her unprecedented trip to live with and study Sioux women on the Rosebud Indian Reservation.

[3] La Flesche gained a position with the Bureau of American Ethnology at the Smithsonian Institution, with which Fletcher collaborated on her research.

[3] In their joint book and articles on the Omaha, La Flesche followed the anthropological approach of describing rituals and practices in detail.

During his regular visits to the Omaha and Osage, and study of their rituals, La Flesche also made recordings on wax cylinders (now invaluable) of their songs and chants, as well as documenting them in writing.

The young composer Charles Wakefield Cadman was interested in American Indian music and influenced by La Flesche's work.

In 1908 La Flesche proposed a collaboration with Cadman and Nelle Richmond Eberhart, to create an opera based on his Omaha stories.

[5] Beginning in 1910, La Flesche gained a professional position as an anthropologist in the Smithsonian's Bureau of American Ethnology, serving there until 1929.

[7] Contemporary Osage tribal members have compared the effect of hearing the recordings of their traditional rituals to that of Western scholars reading the newly discovered Dead Sea Scrolls.

[6][9] For most of his years in Washington, La Flesche shared a house on Capitol Hill with Alice Fletcher, with whom he worked closely, and Jane Gay.