The Duk Lost Boys Clinic is the first of its kind in southern Sudan's Duk County and will offer treatment to more than 150,000 people when it opens later this year.
The clinic is the brainchild of John Dau, who recently appeared in God Grew Tired Of Us, a documentary about 25,000 "lost boys" who fled from war-torn Sudan to Kenya.
The documentary, which was co-produced by Pitt, won two prizes at last year's Sundance Film Festival.
Dau said: "Angelina Jolie and Brad Pitt demonstrate the American spirit of generosity. Hopefully their donation will inspire others to join with us to rebuild southern Sudan."