The church has a history dating back to 1513 when the Portuguese signed a treaty with the Zamorins. With the permission of the Zamorins, the Portuguese built a factory in Kozhikode and a church, dedicated to the Virgin Mary of Immaculate Conception. The church was then known as Matri Dei. The setting up of this church ushered in a new era for the Catholic congregation of Calicut Diocese.The Archbishop of Goa, Dom Alexis de Menezes, visited Kozhikode in 1599 and met the Zamorin. Later, he sent more Jesuits to Kozhikode to renovate the chapel with the Zamorin's help.In 1724, the Zamorin entered into another treaty with the Portuguese, upon which he promised all support to complete the renovation of the church. The church was rebuilt with stone and mortar. A vestry, a belfry and porches were added to the structure. In 1923, the church became the Cathedral of the Diocese of Calicut.