The establishment of St. Roch Parish began in 1911 when the Archdiocese of St. Louis purchased land at Waterman and Rosedale streets for the sum of $55.00 a square foot. Rev. George P. Kuhlman was named the first pastor of St. Roch.

On September 17, 1911, in a small store at 6008 Kingsbury, the first Mass of St. Roch Parish was celebrated.

In 1912, a school building was constructed at the cost of $50,000. It contained a chapel on the top floor, four classrooms on the second floor, and living quarters for the pastor, Fr. Kuhlman.

In 1913, the Sisters of St. Joseph began teaching 45 children in the school. The first lay teacher was not hired until 1928. The rectory was completed in 1915 which freed up space for more classrooms in the school building.

The year 1916 brought the Rev. James Downes as an assistant to Fr. Kuhlman and 120 students enrolled in the school. The groundbreaking for the Church occurred in 1921. In this same year, Rev. William T Glynn replaced Fr. Downes. Unfortunately Fr. Kuhlman died in 1922 and did not see the completion and dedication of the new church that year. Rev. John Spencer succeeded him as pastor.  In 1926, Rev James Beggan became Fr. Spencer's second Assistant.

In the 1920s, with the completion of the church, several service organizations were established. Boy Scout Troop 98 was chartered in 1920 and Fr. Downes became the first Scoutmaster. Later in 1926, Dr. Forrest Staley "Doc" assumed the Scoutmaster duties. In 1921, the Mother's Club which is now the basis for the Parent Teacher Association began. With an early focus on serving the poor, the St. Roch Conference of St. Vincent de Paul Society was organized in 1923. The beginning of the Immaculate Conception Sodality for Women which was later called the Religious Activities Committee first met in 1924. The Ushers and Altar Societies had informal beginnings in 1928.

During the decade of the 1930s, several events occurred: the formation of Girl Scout Troup 104 (1932); Rev James P. Flood replaced Fr. Glynn as Assistant (1938), and a four family flat at the corner of Waterman and Rosedale was remodeled as a convent for the teaching Sisters (1939). Prior to the development of the convent, the Sisters had been commuting from 18th and Cass Avenue to teach at the school.

The 1940s brought about some changes at the Parish House. Rev. George A. Lodes replaced Fr. Beggan as Assistant (1943). Rev. John Phelan replaced Fr. Flood as Assistant and also Rev. Joseph T. Schejbal arrived to assist an ailing Msgr. Spencer in 1947. Rev Robert J Dwyer began a one year stay at St. Roch in 1948. Another significant event in terms of parish administration was the establishment of the Parish Councils of Catholic Women and Men in 1948.

Increased activity took place within St. Roch Parish in the 1950s. Msgr. Spencer died after 28 years of service at St. Roch. Rev Sylvester Tucker replaced Msgr. Spencer. Bells began to chime from the Church tower in 1955 when Fr. Tucker had them installed. Fr. Lodes left as Assistant (1956) and was replaced by Rev William Lyons. Msgr. Bernard O'Flynn became pastor in 1957 following the death of Fr Tucker. Rev James Holland assisted at St. Roch while serving as administrator of Corpus Christi High School. The parish complex expanded with the purchase of two apartment buildings behind the Church. The buildings were demolished to make room for the parking lot/playground (1957.)

Development of the school property and change were the theme for the 1960s. Msgr. O'Flynn bought two buildings east of the school (1960). Rev Robert M Peet replaced Msgr. O'Flynn as pastor in 1962. In 1963 the "new" school building was dedicated, adding more classrooms, offices and a gymnasium to the parish complex. The church was also remodeled following the directives of Vatican II (1964). Rev Paul Kaletta arrived as Assistant Pastor in 1960. Rev Edmund Griesedieck replaced Fr. Kendrick (1964.) The number of priests serving the parish increased further when Rev Raymond Hampe and Rev Joseph Ryan came in 1969. Significant parish events included the first Parish Homecoming (1960), the Parish assembly meeting for the first time (1966), an outreach mission opened on Kingsbury (1966) and the parish joined the Skinker-DeBaliviere Neighborhood Association (1966.)

The decades of the 1970s, 1980s and 1990s brought many personnel changes. In 1971, Rev. Edward J O'Donnell and Rev. Michael Palmer joined the parish and Rev. Joseph Pallikkathoyil became an assistant. Rev. Al Rocklage began two years of service in 1973. Rev. John Fleming came to St. Roch in 1976. Rev. Campbell joined the parish for five years in 1979. In 1981, Rev. Salvatore Polizzi replaced Msgr. Peet as pastor. Rev. Robert Samson was assigned as Assistant to Msgr. Polizzi in 1985. Rev. Paul Rothschild replaced Fr. Samson in 1990. Rev. Lawrence replaced Fr. Samson in 1990. Rev. Lawrence Herzog was in residence not as an assistant in 1991. Rev. John Borcic came in residence not as an assistant in 2008. Rev. Robert McDermott came in residence.

Improvements were made during this time to both the school and the church building. In 1985, the Church Hall was totally renovated and a chair lift was installed. A sheltered walkway was constructed to connect the two school buildings in 1999. The interior of the church was repainted in 1999.

St. Roch welcomed the 21st century and hosted a school reunion in 2000. St. Roch school embraced the computer age by becoming one of the most technologically advanced parochial schools in the City of St. Louis with the installation of SmartBoards in 5-8 in 2004, K-4 in 2005, Preschool in 2008, and the Art Room in 2010. Most recently, St. Roch purchased 47 new computers to replace their outdated models.

Remarkably, over the past 100 years of St. Roch School's existence, there have been only 15 principals.

Over the years, there have been many loyal, dedicated teachers that have enlightened the students who have attended St. Roch and they have worked tirelessly to give the students the best education possible.