The first Catholic Parish on the Gulf coast was established at Mobile in 1703, one year after the founding of Mobile. In 1704, Father Henri Roulleaux De la Vente was canonically installed as the first pastor of the Church of Fort Louis de la Louisiane (Mobile). When the City of Mobile was relocated to its present site in 1711, the Parish Church was rebuilt on the West side of Royal street just North of Conti Street, under the patronage of Our Lady of Mobile. It was in 1781, in Mobile's Spanish period, that the parish received its present title “Church of the Immaculate Conception.”

When bishop Michael Portier became the First Bishop of Mobile in 1829, he set out to build a Cathedral befitting the name.