The town is home to St. Francis Xavier University and the oldest continuous Highland games outside Scotland.

Antigonish had been the location of an annual Mi'kmaq summer coastal community prior to European settlement.

[3] The original definition of the name has been lost as the Mi'kmaq language has undergone many revisions over the last two centuries.

Colonel Timothy Hierlihy of the Royal Nova Scotia Volunteer Regiment received a large land grant surrounding Antigonish Harbour.

[6] St. Francis Xavier University was established in Antigonish in 1855, having been founded in 1853 in Arichat, Cape Breton and originally called the College of East Bay after East Bay, Nova Scotia where an earlier institution had once existed (1824–1829).

was originally a Catholic seminary and was granted full university powers in 1866 by an act of the Nova Scotia House of Assembly.

The workforce is primarily white collar with the largest employers being St. Martha's Regional Hospital and St. Francis Xavier University.

Until 2011, Antigonish accommodated Canada Post's National Philatelic Centre, which provided mail-order services for worldwide collectors of Canadian stamps.

It was named as the best primarily undergraduate university in Canada by Maclean's magazine for five consecutive years (2002–2006).