The Roman Catholic Archdiocese of Hartford includes the church as part of its jurisdiction. It stands as the oldest Roman Catholic parish in the state of Connecticut.

In 1829, the founding of Saint Patrick Parish in Hartford made it the first parish in Connecticut, and Italian immigrants established Saint Anthony Parish in the 1890s. The parishes merged in 1958 to create Saint Patrick-Saint Anthony Parish. A fire destroyed the original church from the 1850s in 1875, and another fire partially destroyed the rebuilt church from 1876 in 1956. The combined parish constructed the current church within the walls of the 1876 building. In 1984, as part of a Multiple Property Submission study of Ann Street Historic District Complexes, the main church was listed on the National Register of Historic Places.

The parish, which would evolve into Saint Patrick Parish, was established in 1829 to cater to a surge of Irish immigrants in Hartford, becoming the oldest permanent parish in both Hartford and the state of Connecticut. At that time, the Diocese of Hartford had not yet been established, and Connecticut was under the Diocese of Boston. The parish purchased the old Christ Church Episcopal church building in 1830, relocated it to the corner of Talcott Street and Main Street, and dedicated it as Holy Trinity Church for Catholic worship (this is not the Holy Trinity Church that was established on Capitol Avenue in Hartford in 1903).

John Brady started building the original St. Patrick’s Church at the corner of Church Street and Anne Street in 1850. A fire destroyed the original Holy Trinity Church building on Talcott Street in 1853. Another fire in January 1875 razed the newly built Saint Patrick Church on Church Street. The congregation held Mass in Allyn Hall while rebuilding the church on the Church Street site.

Bishop Thomas Galberry dedicated the second Saint Patrick Church on Church Street on November 19, 1876, and it was consecrated in November 1885. Another fire in 1956 destroyed the interior of the 1876 church. In 1958, the merging of Saint Patrick parish with nearby Saint Anthony parish led to the third rebuilding of the current Saint Patrick-Saint Anthony Church within the walls of the 1876 building’s remnants.

The Italian community of Hartford saw the establishment of St. Anthony’s as their national parish in the 1890s. Angelo Chicaglione, the founding pastor, handed over leadership to his assistant, Edward Flannery, when he returned to Italy in February 1895. The parish relocated to Market Street in 1921, but flooding in 1936 and 1938 significantly damaged the new building. Redevelopment in the 1950s decimated much of the Italian neighborhood served by St. Anthony. The merger of Saint Anthony parish with Saint Patrick parish in 1958 led to the sale and subsequent demolition of the Market Street church building for redevelopment.

In 1990, the Franciscan Friars accepted an invitation to serve at the parish and started an urban outreach ministry.