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Alpha Chi Omega was formed at DePauw University in Greencastle, Indiana on October 15, 1885.^[2] At the time of its founding, five other Greek-letter women's fraternities were already in existence including Kappa Kappa Gamma and Kappa Alpha Theta (1870), Alpha Phi and Delta Gamma (1872), and lastly Gamma Phi Beta (1874).^[3] Notably, Kappa Alpha Theta was also founded at DePauw University.^[3]

In the fall of 1885, Professor James Hamilton Howe, the first Dean of the Music School, invited seven young women from the school to a meeting with the purpose of forming a fraternity.^[2] Those young women were Anna Allen, Olive Burnett, Bertha Deniston, Amy DuBois, Nellie Gamble, Bessie Grooms, and Estelle Leonard.^[2] Howe himself was not Greek, so he consulted with James G. Campbell, a Beta Theta Pi, on the proper procedures for founding a Greek-letter fraternity.^[3] Campbell was thus responsible for laying out the first constitution and by-laws.^[3] This first constitution read: "The object of this fraternity is as follows: To attain the highest musical culture and to cultivate those principles that embody true womanhood."^[3] On February 26, 1886, the fraternity was given its formal introduction by a soiree musical.^[3]