In his first public remarks in Canada, Pope Francis has asked indigenous residential school survivors for forgiveness.
"I am deeply sorry," the Pope said on the grounds of a former residential school in Maskwacis, near Edmonton.
He said his apology is a first step, and that a "serious investigation" into abuses must occur to foster healing.
The pontiff is in Canada to apologise for the Church's role in schools meant to assimilate indigenous children.
The government-funded schools were part of a policy meant to destroy indigenous cultures and languages.
The papal apology was received by applause from survivors in the audience, some of whom travelled far to hear the Pope speak.
Pope Francis expressed "sorrow, indignation and shame" for the actions of many members of the Roman Catholic Church, who ran and operated majority of residential schools in Canada.
The 85-year-old Pope called the schools system a "disastrous error" and asked for forgiveness "for the evil committed by so many Christians" against indigenous peoples.
Bruce Allan, a survivor of one of the residential schools who was in attendance, said it was emotional to hear the Pope's apology, but many are still looking for action from the pontiff.
"I think probably a lot of survivors are quite angry still," Mr Allan told the BBC.
The Pope said he travelled to Canada with a small pair of moccasins gifted to him by an indigenous delegation in the Vatican earlier in the year.
The moccasins, which the Pope was asked to return, serve as a symbol for the children who attended residential schools and never came home.
He said the moccasins also "speak to us of a path to follow", - that of justice, healing and reconciliation.
His remarks were heard by indigenous chiefs who gathered at Muskwa Park alongside First Nations, Métis and Inuit residential school survivors.
Also in attendance were Prime Minister Justin Trudeau and Governor General Mary Simon, the first indigenous person to hold that position.
Prior to his remarks, the Pope met privately with leaders at the local church and led a silent prayer at the Ermineskin Cree Nation Cemetery, where there are marked - and likely unmarked graves - of residential school students.
After his apology, the Pope wore a traditional headdress gifted to him by an indigenous leader as a Cree honour song was sung in the background.
The former site of Ermineskin Residential School, one of the largest in Canada, is the Pope's first stop on his trip - one the pontiff has called "a pilgrimage of penance".
The Vatican sometimes appears to find it difficult to say sorry for historical injustice. There are those still waiting for a complete apology for the failings of Pope Pius XII and the Catholic Church during the horrors perpetrated in the Holocaust, for example.
But when it came to apologising for the way in which Catholic schools stripped the culture from indigenous children who had been ripped from their homes over generations, the Pope's language was unequivocal.
During the speech, as the Pope used the word "sorry" several times and said he begged for forgiveness, some survivors present showed emotional signs of relief, breaking down in tears or hugging.
Pope Francis' pledge to compel Catholics to support indigenous people in Canada may have felt like a step in the right direction for those saying compensation and investment - in ways that would benefit First Nations, Métis and Inuit peoples - will truly help make amends.
His promise to fully investigate what happened stopped short of what some had been calling for - assurances that those who perpetrated the abuse would be held accountable.
But there was acknowledgement from many listening that the Pope had gone some way to try to understand the trauma the Church had caused and the impact that has had today.
Many have called on the Pope to apologise for the role the Roman Catholic Church played in operating up to 70% of residential schools in Canada.
The schools operated from the 1870s, with the last one closing in 1996. In that period, around 150,000 First Nations, Métis and Inuit children were taken from their homes and placed in those schools.
In a landmark 2015 report by Canada's Truth and Reconciliation Commission, survivors spoke publicly about being subject to abuse, illness and malnutrition at residential schools.
More than 3,000 students are thought to have died at the schools. The TRC report called the residential school system a central element of "cultural genocide" against indigenous peoples of Canada.
The Pope's remarks on Monday come at the heels of a historic apology made in April to an indigenous delegation in the Vatican, saying the residential schools caused him "pain and shame".
The Pope returns to Edmonton in the afternoon, where he will visit the Sacred Heart Church of the First Peoples, the first national parish for indigenous peoples in Canada.
He is scheduled to make other public remarks throughout his trip.