Malala, who now attends Edgbaston High School for girls in Birmingham, said it was the happiest moment of her life, in a video played at the Women in the World summit in New York City.
The 15-year-old set up the Malala Fund after surviving an assassination attempt in October, after standing up for her right to go to school in her home country.
She spent hours undergoing major surgery at the Queen Elizabeth Hospital in Birmingham after a bullet which grazed her brain.
The grant of $45,000 (£29,500) will be given to an organisation in the Swat Valley in Pakistan to support the education of 40 girls aged five to 12 who would otherwise be forced into domestic labour.
The organisation, which was not named for security reasons, will offer a safe place for the girls to study as well as financial support for their families.
In a video played to an audience of thousands she said: “Announcing the first grant of the Malala Fund is the happiest moment in my life. I invite all of you to support the Malala Fund and let us turn the education of 40 girls into 40 million girls.”
Hollywood actress and UN special envoy Jolie introduced the video and pledged to give $200,000 to the fund.
She praised the young girl’s courage.
“Here’s what they accomplished,” Jolie said of Malala’s attackers. “They shot her point-blank range in the head – and made her stronger. The brutal attempt to silence her voice made it stronger.”
The Malala Fund supports the education and empowerment of girls in Pakistan and around the world and provides grants to civil society organizations and individuals focused on education.
The fund is run by a board of trustees, including Malala and her family, with the support of the Vital Voices Global Partnership, founded by Hilary Clinton.