The Sesame Workshop and the International Rescue Committee have won a $100m (£75m) grant to help with the "toxic stress" on child refugees.
It will help children in Jordan, Lebanon, Iraq and Syria
Jeffrey Dunn, head of Sesame Workshop, said Syria's refugee crisis was the "humanitarian issue of our time".
"This may be our most important initiative ever," he said.
The award has been made by the Chicago-based John D and Catherine T MacArthur Foundation, which wants to make "big bets" on influencing major challenges.