In 1852, ten men including William Silliman filed a charter establishing the Silliman Collegiate Institute in Clinton, Louisiana. Silliman then purchased six acres and a house that belonged formerly to Thornton Lawson, a local attorney and judge. He also purchased an additional three acres, and gave additional money for the establishment of a college for young ladies. This institution of higher learning began operation in Lawson's former home, with the addition of a study room. Local tradition holds that Mrs. Lawson had held a school for girls in this same home in the 1840s. The 1852 institute, however, was operated as a school by a board of trustees, and continued to operate even during the War Between the States, according to an announcement published in 1865.

But in 1866, the board of trustees put the Silliman campus up for sheriff's sale because of the depressed economy following the war. Once again William Silliman stepped in. He bought the property and donated it to the Louisiana Presbytery in 1866. The Presbyterians decided to continue the school's operation. This institution was known as Silliman College. It was operated by the Presbytery of Louisiana until 1931. Once again, because of the general economic conditions and a decline in the number of students Silliman College closed.

In 1934, there was a move to have the East Feliciana Parish School Board take over the campus and operate it as a public school, but that suggestion came to naught. Instead, the Louisiana Presbyterian Synod used the buildings and grounds of its former college as the site for annual summer conferences. Thus, for a time, Silliman Institute served as a summer campground for Presbyterians from throughout Louisiana. In the 1960s, the cost of maintaining Silliman and holding the conferences became more burdensome.

A group of interested citizens bought the Silliman campus in October 1965, and organized into Silliman Private School Corporation. Against seemingly impossible obstacles a group of parents and patrons banded together, and school was opened in 1966 for grades 1 through 7. In 1967, the school was expanded to include a full high school curriculum. In 1970, a gymnasium was constructed. In 1977, Silliman Institute expanded to include Pre-Kindergarten through 12th grade.

Throughout the years, numerous improvements have been made to the buildings and grounds. A well-equipped science building and a state-of-the-art elementary complex were constructed. Silliman boasts a modern track and football field as well. Thanks to generous benefactors, the entire parking area has been re-surfaced and a building for storage and weightlifting has been added.

Thus, Silliman Institute can boast a proud heritage of providing students the opportunity to gain a quality education that was begun more than 150 years ago.