It was established in 1896 by the Society of Jesus as part of Loyola College, at the request of the English Catholic community in Montreal.

Founded in 1896, Loyola High School began as Loyola College (an eight-year classical college or "collège classique") which assumed responsibility for the English section of Collège Sainte-Marie de Montréal, a French Jesuit school which existed from 1848 to 1969.

Loyola was originally located in an abandoned Sacred Heart Convent on Bleury and St. Catherine Street.

A fire broke out at this location in 1898, forcing the college to move into the former Tucker School on Drummond Street.

In 1988 a decision was reached to erect a new building in order to properly accommodate the student body and to enable the school to offer the curriculum outlined by the Ministry of Education.

Loyola's traditional rivals in athletics are Lower Canada College and Selwyn House School.

The phrase "Loyola y Onaz" typically appears at the bottom, though another variation of the school's coat of arms includes the Jesuit motto "Ad Majorem Dei Gloriam", meaning "for the greater glory of God".

Loyola had reservations about the course's ability to meet its objectives from a relativistic perspective, and applied for an exemption to teach an ERC equivalency course.

Loyola's equivalency course had similar goals as the government's ERC but was structured on a methodology that was more in keeping with its Catholic, Jesuit identity.