On 10 December 1909 it was announced that Government House would no longer be used as a vice-regal residence. On that same day the University of Queensland was established with the then serving governor, Sir William MacGregor, installed as its first chancellor. He moved out of the House in June the following year, and the building and its surrounding grounds became the University's first campus.
The first classes were held in the House in 1911. The University’s student body numbered 83 – including 23 women – and the teaching staff comprised four professors and thirteen lecturers across three faculties of Arts, Science and Engineering. The rooms in the former governor’s residence were adapted for new use as required: the drawing room became the University library, the dining room was used for English lectures and biology classes took place in the private drawing room.
By the 1920s it was clear that the House was not an ideal educational facility. As one mathematics professor put it, “we are housed in a building inadequate in size and unsuitable in design. It is riddled with white ants; leaking roofs are frequent and falling ceilings not unknown”. The unsuitability of the site saw the University of Queensland progressively move to its current home at St Lucia from 1945, but a lack of space simply resulted in the Queensland Institute of Technology (QIT) moving in. QIT (which became Queensland University of Technology in 1989) used Old Government House for classes until the 1960s, when its Gardens Point campus was more established.