Sekulić was born in Mošorin, Bačka, in what is now the Serbian province of Vojvodina. Apart from her studies in literature, Sekulić was also well versed in natural sciences as well as philosophy. She graduated from the pedagogical school in Budapest in 1892, and obtained her doctorate in 1922 in Germany. Her travels included extended stays in England, France and Norway. Her travels from Oslo through Bergen to Finnmark resulted in Pisma iz Norveške / Letters from Norway meditative travelogue in 1914. Her collection of short stories, Saputnici, are unusually detailed and penetrating accomplishment in self-analysis and a brave stylistic experiment. She also spoke several classical as well as nine modern languages.

Sekulić's lyrical, meditative, introspective and analytical writings come at the dawn of Serbian prose writing. Sekulić is concerned with the human condition of man in his new, thoroughly modern sensibility. In her main novel, The Chronicle of a Small Town Cemetery (Кроника паланачког гробља), she writes in opposition to the usual chronological development of events. Instead, each part of the book begins in the cemetery, eventually returning to the time of bustling life, with all its joys and tragedies. Characters such as Gospa Nola, are the first strong female characters in Serbian literature, painted in detail in all their courage, pride and determination.

Isidora Sekulić also wrote critical writings in the areas of music, theatre, art, architecture and literature and philosophy. She wrote major studies of Yugoslav, Russian, English, German, French, Italian, Norwegian and other literatures.

Isidora Sekulić, Književni pogledi Isidore Sekulić (The Literary Views of Isidora Sekulić) Belgrade, Prosveta, 1986.