The singer and actress laid a stone with an inscription “Raising Malawi Academy for Girls” and the motto, Dare to Dream.
“It has always been my dream to train women leaders who can help develop the country,” Madonna said during the event.
The colourful ceremony in Chinkhota village, some 15km (nine miles) from the capital Lilongwe, was attended by education officials and curious villagers.
“I grew up as a poor girl with my mother, I had no chance for good education,” Madonna said.
“It is my aim to see Malawian girls get the right education,” she added.
The pop star was accompanied by her biological daughter Lourdes and her two other children, whom she adopted in Malawi.
Madonna, who funds several initiatives in the southern African country, broke ground and planted a tree in October last year for the school, which will admit 500 girls from poor backgrounds.