Ksenija Atanasijević was born on February 5, 1894 in Belgrade, the youngest of six children to Doctor Svetozar Atanasijević and Jelena Atanasijević, née Čumić, who died while giving her birth. Her father was a well-respected doctor and director of the State Hospital in Belgrade. Her mother's family was related to the famed Belgrade lawyer, writer and politician Aćim Čumić. Twelve years later, her father died. Ksenija's stepmother, Sofija Kondić, who taught at the Women's College (Viša ženska škola) in Belgrade, became her rightful guardian. Kondić was well-qualified to continue Ksenija's education. From Kondić Ksenija received her first lessons in philosophy: she learned quickly and eagerly, and no sooner another tragedy befall on her. Ksenija's older brother was killed in World War I. Ksenija's best friends while growing up were poet Rastko Petrović and his sister, painter Nadežda Petrović. While Ksenija attended the Lyceum, she was also influenced by Nada Stoiljković, her philosophy professor. Stoiljković suggested that Ksenija should take up philosophy with her former professor at Belgrade, Branislav Petronijević, and so, in the autumn of 1918, Ksenija Atanasijevic became Petronijevic's pupil at the University of Belgrade.

Authoritarian and demanding, Petronijević was exactly what Ksenija needed at that point. A brilliant professor and one of the most famous philosophers of his day in Serbia and elsewhere, he was a hard taskmaster. Petronijević's aim was to challenge his pupils to be able to maintain a philosophical discussion with their tutor. Ksenija was one of the most brilliant students ever to attend the university and it was not long before she attracted the attention of Belgrade's most distinguished intellectuals. She graduated in July 1920 with the highest marks in her graduating class, obtaining a university diploma in "pure and applied philosophy and classics." An excellent student, she decided to pursue an academic career in philosophy and soon after graduation, began working on a doctoral thesis on Giordano Bruno's De triplici minimo. She went to Geneva and Paris to seek out rare philosophical works and to discuss her thesis with specialists in the field, and on January 20, 1922, defended her Ph.D with honors in Belgrade before a panel of academics, including rector Jovan Cvijić, Mihailo Petrović, Milutin Milanković, Veselin Čajkanović, and Branislav Petronijević, her mentor. After her thesis was successfully defended, she became the first woman to hold a Ph.D. in Philosophy in Serbia. She was then 28 years old. In 1924, she became the first female university professor to be appointed to the Arts Faculty, Department of Philosophy at the University of Belgrade, where she taught classics, medieval and modern philosophy and aesthetics for twelve years. During her teaching career, she was a committed feminist both in theory and practice. She was a member of the Serbian Women's League for Peace and Freedom, the Women's Movement Alliance, and editor of the first feminist journal in the country, "The Women's Movement" (Ženski pokret), published from 1920 to 1938.

In 1936, she was removed from her university position on trumped-up charges of plagiarism because some of her male colleagues who worked alongside her felt threatened by her exceptional abilities. It was the result of a reaction to the liberal ideas she espoused and promoted and especially to her decision not to become part of an entirely male-dominated, academic ideological clique. Her sense of intellectual autonomy meant that not only was she unwilling to accept conservative ideologies structuring her teaching and writing, she was also capable of criticizing the work of her peers. At the time the Encyclopædia Britannica cited her study, The Metaphysical and Geometrical Doctrine of Bruno, written in French in Paris in 1924 as an authoritative work about an important and often neglected aspect of Bruno's philosophy. Her consequent dismissal caused a considerably outcry in Belgrade among intellectuals. At a public meeting where many people spoke in support of her, the most prominent speakers were law professor Živojin M. Perić and poets Rastko Petrović and Sima Pandurović.