Groundbreaking for the school started on 8 October 1939 and presided by
Romuald Denis Hayes,
Bishop of Rockhampton. The school officially opened in February 1940 with 42 boarders and 17 day students. The first headmaster of St Brendan's was Brother Basil Gettons. The school's spiritual and academic policies are rooted in the traditions of
Edmund Ignatius Rice and the school is a member of
Edmund Rice Education Australia. The school is named after
Saint Brendan the Navigator.
St Ursula's College, Yeppoon, a separate Catholic all-girls day and boarding school located further into the centre of Yeppoon, has shared a close relationship with St Brendan's. Both schools share a relationship with a Catholic primary school in Yeppoon, Sacred Heart. The college song,
Bordered by blue waters splendid, details the rural surrounds of the school near Mary's Mount, as well as confirming strength in faith-based learning. In September 2022, the Christian Brothers Oceania Province announced it would withdraw from St Brendan's College at Yeppoon at the end of the 2023 academic year, ending 84 years of Christian Brothers affiliation. A farewell mass took place August 28, 2023. ==House system==