Although born in Wisconsin, she attended high school in Westfield, Massachusetts. In 1871 she returned to Wisconsin and enrolled in Ripon College, where she graduated in 1874. After graduation she taught in public school for two years and then moved to Milwaukee, where she worked as a journalist. In 1892 she began postgraduate work in history, economics and sociology at Wisconsin State University. She later became a librarian at the Wisconsin Historical Society.
In 1894 Blair resigned from the library staff and became assistant to Dr. Reuben Gold Thwaites. Thwaites was the translator of the 73-volume work Jesuit Relations (1896-1901). This massive work consisted of English translations of the annual reports issued by the superior of the Jesuit missions in New France to the Jesuit overseer in France between the years 1632 and 1673. Blair participated in the editing and annotations. After her work on the Jesuit Relations, she assisted in the editing of the journal of Father Louis Hennepin and of the journals of the Lewis and Clark expedition, still working with Thwaites.
In 1903 she began work on the project she is most remembered for, the translation and editing of Philippine historical documents that were published in the 55-volume series The Philippine Islands, 1493-1898 (1903-09). Her collaborator was Dr. James A. Robertson, later librarian at the Philippines Library in Manila. Most of the documents in this enormous collection had not previously been translated into English. Volumes 15 and 16 consist of Antonio de Morga's History of the Philippine Islands From Their Discovery by Magellan in 1521 to the Beginning of the XVII Century, an extremely valuable source on the early history of the islands.
Her last work was the translation and editing of documents for The Indian Tribes of the Upper Mississippi Valley and Region of the Great Lakes (2 vols., 1911-12). This work included Nicolas Perrot's Memoir: The Habits and Customs of the American Indians. Blair died in 1911, just days after receiving an advance copy of volume 1 from the bindery.
According to her obituary in the Madison Democrat,