Mrs Obama made the comments at a meeting with 10 girls who shared tales of rising early to feed their families before heading off on long treks to school and studying late into the night.
"You are role models to the world," she said, calling on the students to use their voices "to advocate for good things — whether it's more education, better healthcare, more freedoms, more equality.
"You now will have a voice and you will have the training and education to use it for good. Not just here in Cambodia, not just here in Siem Reap, but in the world. I hope that you all will feel empowered to do that."
Mrs Obama's visit to Hun Sen Prasaat Bankong high school near Siem Reap was part of a five-day trip to Asia to promote the US-led education initiative "Let Girls Learn".
She was accompanied to the school by Bun Rany, the wife Prime Minister Hun Sen, who has ruled the country for 30 years and is the frequent target of criticism for rights abuses.
Let Girls Learn, to be run by the Peace Corps, is meant to help get 62 million girls around the developing world back into classrooms."
Read article by The Associated Press from Bangkok Post.