He was interrupted soon after beginning his speech, prompting a majority of those in the audience to cheer the president, who asked for calm and told listening graduates: "We don't do things the easy way."
The AFP news agency said four men heckled the president, shouting "abortion is murder" and "stop killing babies" before being escorted from the auditorium.
Mr Obama laid out his views on abortion in clear terms, describing it as "a heart-wrenching decision for any woman".
To sustained applause, he outlined steps he supported.
Obama has mostly played to favourable audiences since his election
"Let's work together to reduce the number of women seeking abortions by reducing unintended pregnancies, and making adoption more available, and providing care and support for women who do carry their child to term," he said.
The decision to invite Mr Obama to Notre Dame, the largest Catholic university in the US, has been fiercely criticised.
Many activists and Church leaders have directed their ire at university authorities they accuse of betraying Catholic principles.
"It is clear that Notre Dame didn't understand what it means to be Catholic when they issued this invitation," said Cardinal Francis George, president of the US Conference of Catholic Bishops.
Bishop John D'Arcy, of the diocese where Notre Dame is located, said he would boycott the graduation for the first time in his 24 years as bishop, the Chicago Tribune reported.
And conservative critics have described the awarding of an honorary degree as "inappropriate".
Addressing his critics indirectly, Mr Obama told academics and graduates at Notre Dame that he did not want the debate around abortion to go away.
Conceding that the views of opposing advocates were "irreconcilable", he said each side would continue to make its case with conviction.
CATHOLICS IN AMERICA
60 million Catholics in US
49% think abortion should be legal in most or all cases, against 42% who think it should be illegal
50% think it was right to invite Mr Obama to give the Notre Dame speech; 28% think it was wrong
"Surely we can do so without reducing those with differing views to caricature?" he asked.
A strong majority of students were reported to be in favour of the president's visit, but a petition containing some 360,000 names was delivered to the university as a mark of protest.
Overnight, students opposed to abortion rights attended an all-night prayer vigil to protest against Mr Obama's visit, and an estimated 200 people attended a prayer session at Alumni Hall Chapel.
More than 100 protesters gathered and 23 marched on to the campus on Saturday, the Associated Press reported. Police arrested 19 for trespassing, with four also charged with resisting police.
A university spokesman said none of those arrested was a student, AP added.
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