Mrs Obama was close to tears as she addressed the excited crowd at the Elizabeth Garrett Anderson School in Islington, north London.
She told them: "We are counting on every single one of you to be the best that you can be."
Mrs Obama is in the UK with husband Barack for the G20 summit.
Her visit to the North London school was greeted with much excitement by pupils and she sat smiling, riveted, as Year 11 pupil Grace Hollowell and the school's junior choir performed the Whitney Houston hit Believe.