Josefina Niggli was born in Monterrey, Nuevo Leon, Mexico on July 13, 1910. Her father Frederick Ferdinand Niggli was descended from Swiss and Alsatian migrants who had immigrated to Texas in 1836. Frederick moved to Mexico in 1893 and found a job as the manager of a cement plant in the village of Hidalgo. Josephina's mother, Goldie (Morgan) Niggli, was a violinist of Irish, French and German descent.

In 1925 Niggli was sent to San Antonio, Texas, when she was 15 years old to finish her high school education. Afterward she received her B.A. from the College of the Incarnate Word, majoring in Philosophy and minoring in History. She credited Dr. Roehl, head of the English Department at the College of the Incarnate Word, with influencing her to become a writer. During her college years, Niggli published articles in Mexican Life and Ladies' Home Journal. Her early creative efforts earned her prizes both in fiction writing (Ladies' Home Journal) and poetry (National Catholic Poetry Contest). She received her M.A. from the University of North Carolina in 1937. While there she wote a number of plays including her master's thesis, Singing Valley in 1936, the Carolina Playmakers produced Tooth or Shave (1935, 1936), The Cry of Dolores, Soldadera, The Red Velvet Goat, Azteca, Sunday Costs Five Pesos (1936), and The Fair-God (1937).

In 1938 Margaret Mayorga published Niggli's play This Is Villa and Soldaderain The Best One-Act Plays of 1937. In 1939 Niggli began teaching English and drama at the University of North Carolina, Chapel Hill. She also wrote for radio, television and film.