The school was one of several buildings associated with the large Catholic parish others included a church, a rectory, which was adjacent to the church, a convent of the Sisters of Charity of the Blessed Virgin Mary, which was across Iowa Street from the school, and two buildings one block east on Hamlin Avenue referred to by the parish as Joseph Hall and Mary Hall respectively, which housed kindergarten and first-grade classes. Most of the families in the immediate neighborhood were Catholic. The area was also home to several other first, second, and third-generation immigrant groups, including German Americans, Polish Americans and other Slavic Americans. The neighborhood had originally been heavily Irish-American, but gradually developed in the first half of the twentieth century into a largely Italian-American middle-class community. It was located at 909 North Avers Avenue in the Humboldt Park area of Chicago's West Side, on the northeast corner of West Iowa Street and North Avers Avenue (some sources describe the school as 'in Austin'). Our Lady of the Angels was an elementary and middle school comprising kindergarten through eighth-grade education.

The disaster led to major improvements in standards for school design and fire safety codes. The severity of the fire shocked the nation and surprised educational administrators of both public and private schools. Pope John XXIII sent his condolences from the Vatican in Rome. The disaster was the lead headline story in American, Canadian, and European newspapers. Many more were injured when they jumped from second-floor windows which, because the building had a raised basement, were nearly as high as a third floor would be on level ground (c. A total of 92 pupils and 3 nuns ultimately died when smoke, heat, fire, and toxic gases cut off their normal means of egress through corridors and stairways. The elementary school was operated by the Archdiocese of Chicago and had an enrollment of approximately 1600 students.

The fire originated in the basement near the foot of a stairway. On Monday, December 1, 1958, a fire broke out at Our Lady of the Angels School in Chicago, Illinois, shortly before classes were to be dismissed for the day.

To Sleep with the Angels by David Cowan