The oil painting by Jonathan Yeo shows Malala doing her homework.
It's being donated by the artist to benefit the Malala Fund, which campaigns for girls' education.
Christie's New York is offering the portrait on May 14. It's expected to bring USD 60,000 to USD 80,000.
It was painted months after the then-15-year-old Malala was shot as she traveled to school in 2012.
President Barack Obama called Malala the "bravest girl in the world."
She now lives in England.