The establishment of a medical research institute at Mater Hill was a long-term goal of the Sisters of Mercy and the Mater Health Services Governing Board. This desire and commitment culminated in July 1998 with the formation of the Mater Medical Research Institute, a development funded by the Sisters of Mercy and their supporters. The Governor-General officially opened the institute in March 1999. In 2006, Mater Research incorporated and became a National Health and Medical Research Council (NHMRC) accredited independent medical research institute.

Mater Research commenced operation in 1998 with 10 staff. Since then it has experienced significant growth, creating an internationally competitive institute with many original programs attracting top scientists from around the globe.

Mater Research has documented significant outputs in publications, patents, student achievements, collaborations, peer-reviewed funding and other significant funding.

The initial scientific focus for Mater Research was cancer immunology, however the research has grown to seed and attract other independent scientific teams. The institute now has five research programs, closely integrated with the clinical services at Mater Health.

The expansion of the research themes at Mater Research is in part a result of the close and effective working relationship established between Mater Research and Mater Health. Working together on significant joint ventures, including the development of impact project targeting major improvements in health outcomes, confirms the link between medical research and its clinical application and this relationship continues to strengthen.

Mater Research has also proved its capacity to attract funding for ongoing developments and is a proud partner in the Translational Research Institute (TRI), a $354 million facility built on the Princess Alexandra Hospital site. With access to this infrastructure since January 2013, Mater Research has continued to grow rapidly both on the Mater campus and in the purpose built TRI providing world class facilities for our biomedical research.

The University of Queensland, as an affiliate organisation from the institute's inception, is also an increasingly important partner. In 2013, Mater Research and The University of Queensland formalised a long-standing relationship to form the Mater Research Institute – The University of Queensland (MRI-UQ). Merging the clinical expertise and high-quality healthcare of Mater with the research, education and training strengths of The University of Queensland provides strategic and operational benefits to both organisations to benefit healthcare.  The collaborative alliance between Mater Research and The University of Queensland means that Mater Research is also a full institute within The University of Queensland Faculty of Medicine, a global top 50 university.

On 23 April 2013, canonical sponsorship for Mater was transferred to Mercy Partners, which means Mater Research is now owned by Mercy Partners.

2016 saw Mater Research integrate further within Mater, the CEO joining the Mater Hospital Group Executive.  In 2019 MMRI was rebranded as Mater Research Ltd and Professor Maher Gandhi was appointed as the Executive Director of Mater Research and MRI-UQ.  In 2020 the research programs were enhanced with new leadership and alignment to reflect the changing needs of the community.