Starting with the multi-talented Father Henry Brown, Immaculate Conception parish has been blessed with many fine spiritual leaders. Father Joseph Biemans became pastor right after the dedication of the new church, and in 1857 opened a parish school in a rented store building on Gay Street. The school was forced to close in 1861 due to the rigors imposed by the Civil War.
The noted priest-poet, Abram Joseph Ryan. became pastor in 1865 after having served as a chaplain in the Confederate Army. Ranked today as a minor American poet, Father Ryan was renowned in his day throughout the South both as a poet of secular and religious poetry and as a preacher. He remained in Knoxville only two years but he left his mark as a healing figure of the Reconstruction Era.
Father Michael Finnegan was pastor from 1866 to 1872; during that time he expanded the school program and he bought land for, and opened Calvary Cemetery. In 1872 Father Francis Marron became pastor. In order to assess his new parish, Father Marron set out to meet his parishioners, hoping to convince some to move closer to Knoxville. Father Marron distinguished himself as a school and parish administrator. He brought in teaching religious sisters to staff the school, thereby ending the era of lay school masters. He undertook the building of the much needed larger church for the expanding congregation. He stayed until 1899.