For the first 52 years of its existence, the Philomathean Society remained a literary organization exclusive to Wesleyan College. Around the turn of the 20th century, discussions began about becoming a national organization and expanding to other campuses. This change was fiercely resisted by some alumnae, who feared that national expansion would mean the loss of the Philomathean Society's high standards, but their opposition was overlooked when, in August 1904, the Society was charted as the Alpha chapter of Phi Mu Fraternity.
The transfer one of Alpha chapter's members, Virginia Willingham (Wood), to Hollins College in Hollins, Virginia that fall provided the perfect opportunity to establish a second chapter and Beta Chapter was installed on October 4, 1904. A year and a half later in March 1906, Gamma Chapter was installed at Salem College in Winston-Salem, North Carolina. Expansion boomed after that and within the next year give more chapters - Delta, Upsilon Delta, Zeta, Eta, and Theta - were established. To install each new chapter, Alpha Chapter members traveled to each campus to perform the ceremonies. For Theta Chapter, far away in Nashville, Tennessee, the initiation service was sent by mail, and the Theta Chapter members installed themselves!
In 1907, Phi Mu held its first National Convention and approved a rule stating they would "not consider any Seminaries, Institutes, Schools, or D-rank Colleges until we get in three more University Chapters or A-rank Colleges." While some thought it would be easier to accept petitions from the lower ranked schools, it was essential that they maintain high standards if they were to be accepted into the newly formed National Panhellenic Conference (NPC). At the 1910 National Convention, the decision was made to take the necessary steps to gain acceptance into NPC. The first step, however, was to disband the existing chapters at low-ranking institutions. For the good of the Fraternity as a whole, the representatives of Upsilon Delta, Zeta, Eta, and Theta voted to dissolve their own chapters. The decision, though difficult, proved fruitful, and Phi Mu was recognized as a member of NPC in December 1911.
By 1914, ten years after nationalization, Phi Mu had installed 26 chapters. This progress, however, was overshadowed by the stunning blow that Wesleyan College had abolished sororities: Alpha Chapter was no more. Though the loss of Alpha Chapter was a terrible blow, Phi Mu continued to grow in the ensuing years, expanding beyond the south and adding 25 more chapters in the next 10 years.