A crowd of thousands gathered at the Gibson Amphitheatre to listen to him speak and answer questions.
The session lasted nearly two-and-a-half hours and His Holiness focused on finding inner peace.
The talk was organized by Los Angeles-based Whole Child International to raise awareness of the plight of orphaned children.
His Holiness' message was universal: that to create a peaceful society, people need to cultivate compassion at a very young age.
KABC-TV reported that people who attended the speech left the amphitheatre in awe.
"Politics aside, one of the reasons that he is such popular person is because he keeps promoting non-violence and compassion," said Jeff Gilkman. "I think that people are able to rise above politics and take that message and promote those ideas as well."
"I'm ready to go tackle anything now because as long as I keep that inner peace things will be OK," said Genevieve Hayman.
Whilst in Los Angeles, His Holiness talked to The Associated Press about his meeting with US President Barack Obama last Thursday.
He said he doesn't fault President Obama for the low-key reception he received at the White House, because he recognizes that the president must juggle ties to himself with concerns about angering China.
He added that he understands Obama must be practical in exercising his commitment to human rights worldwide.
"No disappointment. The last six decades my heart hardened. I do not consider important political gestures. I don't care. The important is meet face-to-face," His Holiness said.
He also briefly addressed the Tiger Woods scandal and the golf star's public comments on Friday about his adultery and straying from his Buddhist faith.
His Holiness said he did not know who Woods was but that, "I think mainly whether you call it Buddhism or another religion, self-discipline, that's important - self-discipline with awareness of consequences."
The remainder of His Holiness' ten-day US tour will take him to Florida, where he will speak on global compassion and ethics in education.