The construction of Harrison Trimble High School began in September 1960 and was first occupied by classes in September 1961. At that time, the school had 37 teachers and 25 classes with an enrolment of 837 students. HTHS was unique in that it was the first school in the greater Moncton area to have bilingual high school classes in the same building with English students in academic and commercial classes. In the 2024-2025 school year, HTHS has over 100 teachers with an enrolment of over 1,600 students.

The school is named in honour of Dr. Harrison H. Trimble, who was born and educated in Hampton, NB. He is a graduate of UNB and was a star athlete in football, basketball, and track. After having served in the First World War, Dr. Trimble came to Moncton in 1922 and taught at the former Aberdeen High School. In addition, he served as Secretary of the School Board and Superintendent of the Moncton Schools.