St. Anthony had its beginnings as a seasonal fishing station for French and Biscayan (Basque) fishermen in the early 1500's. This is how Jacques Cartier found it in 1534 when he named the protected harbour "St. Anthony Haven". During the eighteenth century, many French and English vessels came each summer to fish on the rich banks of the White Bay Coast. During the latter decades of the nineteenth century, St. Anthony served as a service point for Newfoundland schooners sailing to and from the Labrador coast from ports in Bonavista, Trinity, and Conception Bays.

Between 1891 and 1901 the population of St. Anthony showed an unusual increase of 67 percent, rising from 139 to 233 individuals. This increase can only be attributed to the arrival of Sir Wilfred Grenfell on the coast in 1892, and his selection of St. Anthony as the site for the hospital and missions which he established. By 1911, the population had virtually doubled to 462 persons in the town. The establishment of the mission founded by Sir Wilfred Grenfell in 1893 began the development of St. Anthony as an institutional and medical centre. These developed to such a degree that they must be considered one of the more important facets of the town's economy today.

In 1945 the Town of St. Anthony became incorporated. At this time it had a population of 946 and by 1951 it had increased to 1380. This large increase in fishing in the area was due in part to the construction of a United States Defense Station 1951, which was completed in 1953, and the opening of a fish filleting plant by Fishery Products International Limited in the early 1950's. Today the Charles S. Curtis Memorial Hospital is the largest employer in the town. St. Anthony is known as the "Iceberg Capital of Newfoundland" and the very northern tip of Newfoundland is the most accessible region to view such a high number of icebergs; beginning in late spring, often lasting until mid-summer, massive sized icebergs are common sightings along our coasts, and often float right into the harbours.