While Qrendi formed part of the parish of Żurrieq, in 1575 its main church was dedicated to the Nativity of Mary. Sometime later, in 1594, it was rebuilt by the people of the village and was rededicated to the Assumption of Mary. During his second pastoral visit, Bishop Baldassare Cagliares declared Qrendi a separate parish, uniting to it the two small communities of Ħal Lew and Ħal Manin. This took place on 15 February 1618 with the consent of Rev. Nicola Bonnici, the parish priest of Żurrieq.
As often happened, the church identified to serve as the parish church later became inadequate for the daily religious needs of the parishioners as these began to grow in number. This created the need for modification, enlargement or replacement of the original church, when Reverend GioMaria Camilleri thought of building a new church. The site chosen was the land on which two small churches stood next to each other, one dedicated to the Assumption of Our Lady and the other to St Anthony.
The work on the new parish church started in 1620, and with the contribution of the community the construction was concluded thirty-five years later, in 1655. While the church was still being built, a pastoral visit took place by Bishop Miguel Juan Balaguer Camarasa, following his consecration as Bishop of Malta in February 1636.
In 1668 work started on the belfry known as ‘Tal-Agunija’ (Agony), which took eleven years to complete. Thus by 1679, and during the administration of the parish priest Rev. Marco Bellia, the parish church was ready and the parishioners could enjoy their new completed church.
With the advent of Rev. Domenico Formosa, a native of Qrendi, the parish church was once again demolished so that a more spacious edifice could be built. The plan for the new church was the work of Lorenzo Gafà.
Don Domenico appears to have been quite an inspiration to his parishioners. He encouraged the villagers to contribute to the construction of the church which began in 1685 and continued till 1691, stopping for a number of years and then resuming in 1695. According to Ferres, who was writing in the mid-nineteenth century, the sacrifices made by the Qrendin to build their church were without comparison in the history of the Maltese Church. One example of extreme sacrifice was the parish priest himself. According to Ferres it was on 17 January 1699 that Don Domenico wishing to encourage his parishioners to do more towards the construction of the church thought of lending a hand so as to lead by example. He grasped a stone, put it on his shoulder, and thus burdened climbed up a long ladder. On reaching the top, while Don Domenico was stepping on a plank of the scaffolding he tripped and fell to the ground dying on the spot.
The edifice of the church was completed in 1712.