He has been labelled as a key architect of the Canadian Indian residential school system by contemporary news sources,[1][2][3] which has been considered an instrument of cultural genocide.

When Taché suggested creating a new vicariate in the Mackenzie River basin, Grandin made an extensive tour of the missions in the area, and worked on the logistics of supply. "

[5] Grandin was an early supporter of the Canadian Indian residential school system and believed that Indigenous Peoples faced extinction and that the best way for them "to become civilized" and to avoid destruction was to educate the young with the "consent of their parents.

"[7]: 159  In 1880 he wrote a letter to then Public Works Minister Hector-Louis Langevin explaining that boarding schools were the best way to ensure children "forget the customs, habits & language of their ancestors".

They foresee well enough the future which awaits them and often beg of us to take them so that we can prepare them for a better prospect.”[7]: 159  In a letter to Canada's first prime minister, John A. Macdonald, Grandin stressed the "success" that had been achieved at the missionary boarding schools, and reported, “The children whom we have brought up are no longer Indians & at the time of leaving our Establishments, the boys at least, do not wish to receive even the ordinary grants made to Indians, they wish to live like the whites and they are able to do so.” He proposed for the government to “make a trial of letting us have children of five years old and leaving them in our Orphan Asylums & Industrial schools until the time of their marriage or the age of 21 years.” For that cause, he made the trip to the nation's capital city, Ottawa, to lobby the government and upper echelons of the Catholic bureaucracy directly.

He also presided over the development and expansion of the Diocese of St. Albert, including the founding of new missions and churches throughout Alberta and the construction of hospitals and schools, which, unusually for the time, were administered by members of female religious orders and lay clergy.

Grandin's spiritual writings were approved by theologians on 20 November 1935, and the cause for his beatification was formally opened on 24 February 1937, granting him the title of Servant of God.

"[13] In June 2021, after the discovery of possible unmarked graves of Indigenous children on the grounds of a former residential school site in Kamloops, British Columbia, Edmonton and St. Albert city officials, as well as private businesses, began removing his name in reaction to a strengthening public condemnation of his role in creating the Indigenous residential school system.