Prior to the opening of the school, students from those towns had attended Southern Regional School District in Manahawkin. Constructed on a site covering 79 acres (32 ha) at a cost of $9.7 million (equivalent to $43.0 million in 2025), Pinelands Regional High School officially opened on September 5, 1979, as a Junior-Senior High School, originally housing grades 7–11 from Tuckerton, Little Egg Harbor, Bass River, and Eagleswood, while seniors finished their education at Southern Regional.
The building originally housed grades 7–8 on the third floor, 9–10 on the second, and 11–12 on the first. During the first school year (1979-1980) there was no senior class, as those students were allowed finish the year at Southern Regional High School. The building featured an experimental "open classroom" design, where a large group of students of varying skill levels would be in a single, large classroom with several teachers overseeing them; and contained no interior walls. However, this format didn't last long, and in the 1980s, the rooms were walled off, and separated by floor-to-ceiling folding partitions.
In 1991, Pinelands Middle School opened across the street for students in grades 7–8. Also in the 90s, a new building was completed next to the high school, which houses a daycare center called "Rainbow Express". Students taking Child Care classes go to class in this building to help with the daycare kids. In 2002, the Middle School was expanded and the 9th grade was moved there. When the expansion was completed at the Middle School, it was renamed "Pinelands Regional Junior High School" while the High School was renamed the "Senior High School", although this name is rarely used.