Prior to the amalgamation of the Greater Brisbane Council in 1925, Clayfield was part of the Town of Hamilton, described in one contemporary history as "the most picturesque suburb of Brisbane". Originally accessible from the city only by bus and horse tram, the opening of the Sandgate (1882) and Pinkenba (1897) railway lines and the construction of the tramlines to Ascot and Clayfield at the turn of the century were largely responsible for the rapid development of the area. By the 1920s, Clayfield was well established as one of Brisbane's more elite residential suburbs, and the district was well served by schools and churches.
Although Catholic churches were established in Wooloowin (1886), Nundah (1905), and Hamilton (1914), the Catholic residents of Clayfield expressed a desire to Archbishop Duhig for a church of their own during the years of World War I. In response, in 1917, Duhig purchased three acres of land on Widdop's Hill at Oriel Road, Clayfield, which "commanded a very beautiful view of the Brisbane River and surrounding districts, and also of Moreton Bay" and donated it to the parish. A timber church school designed by T.R. Hall was opened on the site by Duhig on 29 September 1918 and came under the care of Father Walsh, parish priest of Wooloowin. At the opening, the Archbishop noted that despite the "strenuous efforts" of the church, he was "unable to keep pace with the increasing need for more accommodation" of Brisbane's Catholic population. At this time, St Stephen's Cathedral was overflowing during each of the six masses held on Sundays. The proximity of the site of St Agatha's to the tramline on Oriel Road made it easily accessible to its parishioners.
The first St Agatha's Church, named for the patron saint of the sixth century church attached to the Irish College in Rome, was one of many timber church-schools constructed by Duhig to meet the urgent need for more places of Catholic worship in Brisbane. These buildings were gradually replaced by more substantial structures, such as the present St Agatha's.
The foundation stone of the new church was laid by Duhig on 10 August 1924. A sum of £1,150 was collected at the ceremony towards the cost of the building. This amount had increased to £2,400 by the church's opening. Donations ranged from small amounts to £200, including £25 from Hennessy and Hennessy, and £25 from Mrs T.C. Beirne. The church was built by S.S. Carrick of South Brisbane at a cost of £10,000. At the time of the opening ceremony, the church was not fully completed. “Shipping trouble” and a shortage of skilled labour caused building delays.
A presbytery was also built around this time to accommodate Father Frank O'Connell who was appointed Parish Priest of Clayfield in 1921. He remained in this position until his death in 1940, and was responsible for guiding St Agatha's from its infancy to a thriving parish containing a convent, Christian Brothers' secondary and primary schools. The adjoining property of Stanley Hall, a private residence dating from the 1880s, was purchased in 1926 by the Presentation Sisters who established St Rita's College there.
Extensive additions, designed by parish priest, Right Rev Monsignor John English, were carried out on the church in 1959, including a large domed sanctuary with adjoining sacristy, altar boys' room, and two side chapels. The original timber church-school is no longer on the site.
Today, St Agatha's Church remains a centre of Catholic education and worship which serves both the local community of Clayfield and the wider community of Brisbane.