This is one of the oldest churches in Gozo, reported to have been in existence in 1400. However, the chapel was rebuilt in 1601 and included an adjacent cemetery and zuntier or front church yard. It subsequently became the first parish church of Xaghra on 28th April 1688 when Bishop Cocco Palmieri created three other parishes in Gozo. The church continued to serve as parish church until 1692.

After the plague of 1814, which carried 104 victims, certain articles within the church were burnt in order to disinfect the place. The present painting, depicting St. Anthony with the people of Xaghra living under tents during the plague, was painted by Dun Salv Bondi` in 1816. The church suffered damage during the 2nd World War of 1939-45. It was repaired and re-consecrated in 1947 under Bishop Giuseppe Pace, who was known for his devotion to St. Anthony. Gozo's famous sculptor Wistin Camilleri then made a new statue showing St. Anthony surrounded by animals.

Since 1948 the feast of the Saint, which falls on the 17th January, has included the very popular and attractive ceremony of the blessing of pets and animals. The tiny square in front of the church is on that day well decorated. That morning the Bishop delivers Mass and blesses a number of rusks (known as the Bread of St. Anthony), and a quantity of oats, both representing a traditional ritual connected with charity. The feast is ended with a procession from the Collegiate Church of Xaghra to that of St. Anthony. Arrived in front of the church the Bishop blesses numerous pets and animals, which usually include; cattle, horses, ponies, donkeys, dogs, rabbits, kittens, guinea pigs and birds. Following the blessing, the owners are given a symbolic memento comprising of a picture of the Saint, a bag of oats, and a rusk.