Formerly known as the County of Sydney, the County of Antigonish was renamed by an Act of Parliament in 1865. The smallest county in the province, it is situated in the north east of Nova Scotia proper. It is nearly triangular in form, the base of the triangle being bounded by the Gulf of St. Lawrence and the Bay of St. George, while the apex is wedged between the Counties of Pictou and Guysborough.

The town of Antigonish was incorporated on January 9, 1889. Leonard C. Archibald, a prominent business man, served as the first mayor, and Rupert Cunningham held the position of town clerk. The early commercial and industrial life of Antigonish depended mainly upon the surrounding farm area. It had a dairy, bakeries, machine shops, woodworking factories, contracting firms and a quarry and monument works as well as shops, banks and service industries.

A post office was established in 1816 long before the town was incorporated, and a telegraph office on July 19, 1852. The Eastern Extension Railway opened for traffic from New Glasgow to Antigonish in September, 1879, and from Antigonish to the station at Crittenden's Creek in December, 1880.

According to the Eighth Census of Canada, between 1871 and 1941 the population of Antigonish and its surrounding county dropped from 16,512 to 10,545. In 1941, more than 72% of the inhabitants were originally from the British Isles; a majority of these were from Scotland or were descendents of Scottish immigrants. A further 22% of the total population was originally from France. The principle religious denominations were Roman Catholic (86.5%), United Church of Canada (6.8%) and Presbyterian (3%).

True to its Scottish roots, Antigonish bustles with activity each summer during the annual Highland Games. The first Games were held in 1863 and sponsored by the Highland Society which had been established on August 22, 1861 by Dr. Alexander McDonald, a pioneer physician of Antigonish County.

St. Francis Xavier University was founded as a college in 1853 in temporary quarters at Arichat, Richmond County, but two years later was transferred to Antigonish. An engineering school was established in 1899 and the first science graduates were granted degrees in 1904. Mount St. Bernard College for women was affiliated in 1894 as was St. Martha's School of Nursing in 1926. In 1906 St. Martha's Hospital opened at Antigonish and had a 180 bed capacity.