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Semple was born in Louisville, Kentucky, the youngest child of Alexander Bonner Semple and Emerine Price. As her father was a prosperous businessman, Semple began her life in the comfort and security of the upper middle-class. In his 1933 memoir of Semple published in the Annals of the Association of American Geographers, Charles Colby wrote about her childhood, “Ellen Churchill Semple came from a fine family and lived her girlhood in an atmosphere of wealth and refinement. … The business [of her father] prospered and thus the family was able to give the children good schooling, an abundance of books, and a healthy, well-ordered life.” As her parents separated when she was young, Semple was raised by her mother, whose high expectations for her children were a motivating factor in Semple’s early education. Semple’s first book is dedicated to her mother, with the inscription: “To my mother, who has always given to her children and demanded from them the best.” Semple flourished at the public and private schools she attended in Louisville, and in 1878 she entered Vassar College at the age of 15.

Semple received both her bachelor’s and master’s degrees from Vassar. After studying classics, English composition and history, she graduated with her bachelor’s of arts degree in 1882 and was valedictorian of her class at the age of 19. Semple taught classics at her sister’s school in Louisville until she returned to Vassar for her master’s, which she received in 1891. On a trip to London, Semple met Duren John Henderson Ward, an American who had studied at the University of Leipzig. Ward introduced her to the writings of Friedrich Ratzel, the founder of anthropogeography (what is now generally called human geography), and after completing her master’s, Semple set off for Germany to study under Ratzel at Leipzig. Semple and Ward exchanged numerous letters and even talked of marriage, but Semple ultimately decided it would not be possible to combine marriage and a career and cut off contact with Ward. Similarly, Colby’s obituary of Semple records her decision to enter academia: “[The period between her degrees] taught her, for example, that social life, while pleasant, could not command her full and continued interest. She tried teaching for a time, but soon realized that teaching alone was not sufficiently challenging for a mind as active as her own.” These examples demonstrate that Semple's career was fundamentally important to her, which was perhaps unusual for a woman in her time, even requiring that she sometimes make what might have been significant sacrifices.

At Leipzig, Semple was not allowed to matriculate at the university because she was a woman, but she still benefited from the instruction of Ratzel and other top professors during her time there in 1891-92 and 1895. Ratzel had a profound influence on Semple’s work, both in encouraging and critiquing her early work and in influencing her thought. Ratzel's influence was important in turning Semple’s interest from history, a focus of her bachelor and master’s work, to geography. Two publications that exemplified Ratzel’s influence on her work were her article “The Anglo-Saxons of the Kentucky Mountains: a study in anthropogeography,” published in 1901 in the Geographical Journal, and her first book, American History and its Geographic Conditions, published in 1903. Arguably the most significant contribution Semple made to the spread of Ratzel’s ideas was her second book, Influences of Geographic Environment, published in 1911. In her introduction to the book, Semple explains how the book is a sort of translation of Ratzel’s foundational book Anthropogeographie, reworked and reorganized to make more sense to an American audience.