In the year 1920, the late Lt. Governor Vicente Villanueva established a general high school named Larena High School with only one section in the first and second year levels and only two teachers including the principal. This school was under the supervision of Negros Oriental High School in Dumaguete City. Since the school had no building of its own, classes were held in the old municipal building which was burnt down during the World War II. After finishing the second year level of high school education, the students who were fortunate enough continued at the Negros Oriental Provincial High School in Dumaguete City while others had to stop schooling. This situation ended in 1929-1930 when the school started operating as a full secondary school, until the outbreak of World War II. The school was then called the Larena Sub-Provincial High School with only four teachers including the Principal. It turned out its first graduates during the school year 1930-1931. At that time it was the only high school in the island, thus enrollment continued to rise.

The following served as principal of then Larena Sub-Provincial High School namely Mr. DionesioNocete, Mr. Esteban Jose, Mr. PelagioVillarin, Mr. Proceso Castro and Mr. Amado Villarin.

Pursuant to Republic Act No. 2423 authored by Lamberto L. Macias with the support of then Governor Eulogio M. Omictin Jr. and implemented by the Bureau of Public Schools, the school was converted into the Larena National Vocational School on July 1, 1960 with Mr. Fabian S. Tuates as the first Principal. The Secondary Trade Curriculum had an enrolment of 146.

On April 14, 1983, the dream of the administration for a full conversion of the school into a college was realized when Parliamentary Bill No. 1303, authored by then Assemblyman Dominador M. Pernes, was approved by the National Assembly as Batas  PambansaBlg. 387 changing the name of the school into Larena National Vocational College.

          This law authorized the offering of collegiate courses supervised by the Department of Education, Culture and Sports. With the help of then Assemblyman Manolito L. Asok, DECS Order No. 39. 1985 came into being granting government recognition to Larena National Vocational College to offer the four-year Bachelor of Science in Industrial Education (BSIE) of the Bureau of Higher Education, DECS, Region VII, CentralVisayas. Dr. Tirso L. Tan, Sr. was          appointed as the first administrator of the college. He was later promoted as the first Vocational School Superintendent.

Through the joint efforts of Hon. Orlando B. Fua, Sr., the Representative of the Lone District of Siquijor, Hon. Miguel Romero of the Second District of Negros Oriental and the constituents of Siquijor, House Bill No. 412 was enacted into law by His Excellency President Fidel V. Ramos on March 3, 1995 through Republic Act No. 7947. This law authorized the college to offer additional courses in addition to its existing curricular offerings. These higher technological courses include degrees leading to Bachelor of Science in Civil Engineering, Education, Forestry, Nautical, Physical and Natural Sciences, and such other collegiate and/or degree courses that may be approved by the Board of Trustees of Siquijor State College.

With its conversion, Siquijor State College is governed by a Board of Trustees. It is composed of the Chairperson of the Commission on Higher Education as Chair, the President of Siquijor State College as Vice-Chair, the Chair of the Committee on Education of the Senate, the Chair of the Committee on Higher and Technical Education of the House of  Representatives, the Regional Director of the National Economic and Development Authority (NEDA), the President of the Faculty Association, the President of the Supreme Student Council, the President of the Alumni Association, two (2) prominent citizens representing the private sector who have distinguished themselves in their professions or fields of specialization and the Regional Director of the  Department of Science and Technology (DOST) as members.

On November 30, 1995, Dr. Tirso L. Tan, Sr. was appointed as the first President of Siquijor State College by His Excellency President Fidel V. Ramos. After he retired from the service on December 31, 1999, Dr. Rosita T. Bidad, the  Vice-President for Academic Affairs took over the school as Officer-in-Charge from January 1, 2000 until August 15, 2000. On August 16, 2000, Dr. Dominador Q. Cabanganan was appointed as the second President of the college. On August 21, 2008, Dr. Baldomero R. Martinez, Jr. was appointed as the third president. On August 19, 2013, Dr. Maria Imogen T. Quilicot was   appointed as the fourth and first woman president..  On October 2, 2017, Dr. Maria Imogen T. Quilicot’s second term of presidency was confirmed by the Board of Trustees.

Siquijor State College is mandated to perform in four core functions in Instruction, Research, Extension and Production. The College President is assisted by two designated Vice-Presidents, the Vice-President for Academic Affairs and the Vice-President for Administration and Finance, Deans, Directors, and members of the Faculty and Staff.