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The parish of St. John Chrysostom was established in 1899, breaking from the parish of St. Augustine. The Rev. Bernard F. Brady was its first rector. St. John's served a mostly Irish immigrant congregation in a neighborhood that had a large Jewish population from Russia, Bohemia and Poland. In 1913, there were about 1000 members. By the mid-twentieth century, the area demographics evolved for a new group of residents who were mostly Latino (from Puerto Rico and the Dominican Republic), as well as African Americans. In the 1970s and 1980s, the area around the church was considered part of the 'Fort Apache' section of the South Bronx, where violence was at an all-time high and many buildings surrounding St. John's were burned. Throughout this time, St. John's remained open and became a safe haven for children.

Built of orange brick with stone trim, the twin-towered church building opened in 1900. The schoolhouse, of similar material, was built in 1914. The Dominican Sisters of Sparkill have staffed the parish school since its opening in 1914.