The announcement came Wednesday at a meeting of the club's board of directors. Winfrey is a native of Kosciusko, Miss.
Winfrey was last in Kosciusko in 1998 when a Habitat for Humanity home was dedicated in her honor.
Past president Paul Powers said the foundation had helped get the Boys and Girls Club program started.
Powers said the 30,000 square-foot facility will be located on eight acres provided by the city near the Jason-Niles Park. Plans are to break ground on the project Oct. 1.