Notre Dame-Siena College of Polomolok, then known as Notre Dame of Polomolok was founded and granted permit to operate in the Poblacion of Polomolok, South Cotabato on July 11, 1966. The recognition for the first and second year high school was granted by the Bureau of Education on July 1, 1968 while the third and the fourth year recognition was on July 7, 1969.
It was founded by Rev. Mother Natividad Pilapil, O.P., the Superior General of the Congregation of the Dominican Sisters of St. Catherine of Siena upon invitation of Bishop Quintin Olwell, C.P., D.D. and the Passionist Fathers. Another prime mover of the foundation was Mr. and Mrs. Roman Anastacio who donated one hectare of their farmland adjacent to the four hectares of land bought by the Congregation. The school building was constructed and made ready for the opening of classes in June 1965.