Harper's meeting with the pontiff at the Vatican wraps up nearly a week of travel for the Canadian leader, including his participation at the G7 summit in Germany.
Harper did not, however, ask the pope to apologise for what a truth and reconciliation commission report recently called the "spiritual, cultural, emotional, physical, and sexual abuse" of students at Church-run institutions.
Canada's aboriginal affairs minister, in advance of Harper's visit to the Vatican, sent a letter to the Holy See outlining the truth and reconciliation commission's 94 recommendations, including the call for a papal apology, which is widely supported by Canadian tribal chiefs.
Many former students alleged abuse by headmasters and teachers, who stripped them of their culture and language.
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At least 3,200 students never returned home.
The experience has also been blamed for gross poverty and desperation in native communities that has led to abuse, suicide and crime.
Most of Canada's Indian Residential Schools, modeled after US Indian industrial schools of the period, were shut down in the 1970s. The last one closed in 1996 in Saskatchewan province.
Harper also invited Pope Francis to attend Canada's 150th anniversary celebrations in 2017, said the prime minister's office said.