The Universitas 21 Deans and Heads of Health Sciences network was established to provide Faculty within U21 member universities with a framework for exploring opportunities for collaborative research, information exchange, and sharing of resources.

Following a successful inaugural meeting of the U21 Deans and Heads of Medicine and Nursing in Singapore in 2000, membership expanded to include Dentistry and Health and Rehabilitation Sciences at the group's second annual meeting in Vancouver in 2001.

In Hong Kong in 2002, members reaffirmed the many opportunities for collaboration and sharing within and across disciplines, and it was resolved that a Secretariat would be established to facilitate a range of projects and initiatives. The University of Melbourne agreed to host the Secretariat and did so for 8 years until it moved to Tecnologico de Monterrey in September 2010. From December 2011 to September 2017, the secretariat was hosted by the University of British Columbia. Since October 2017, it has been hosted by the University of Birmingham.

At the group's fourth annual meeting in Glasgow in 2003, the group's newly-formed Executive Committee was expanded to include representatives from all four disciplines. The U21 Health Sciences membership continued to expand to include Pharmacy (2004) and Public Health (2007). Each discipline is represented on the Executive Committee.

Since 2003, subsequent annual meetings have been hosted by The University of Queensland (2004), Lund University (2005), The University of Nottingham (2006), The University of Hong Kong (2007), The University of Virginia (2008), Tecnológico de Monterrey (2010), Korea University (2011), The University of Auckland (2012) and University College Dublin (2013), Fudan University (2014), Pontificia Universidad Catolica de Chile (2015) and University of Birmingham (2016) and University of Johannesburg (2017).

The next meeting of the U21 HSG will be hosted by the University of Melbourne on 10-14 September 2018.