Brenda Niall's schooling was at Genezzano in Kew, Victoria. After obtaining her B.A. at the University of Melbourne, Niall transferred to the ANU, where she gained her M.A. In 1964 she was appointed as a teaching fellow in the English Department at Monash University and was promoted to Senior Lecturer in 1975 and Reader in 1994. At Monash she also completed her PhD. Dr Niall has held visiting fellowships at Michigan and Yale Universities. She was American Council of Learned Societies Visiting Research Fellow in 1975 and Visiting Scholar, Humanities Research Centre at the ANU in 1983 and 1987.
Dr Niall retired from her position as Reader in English Literature at Monash University in 1995. Her research interests are in the fields of Australian Literature (in particular Martin Boyd, Ethel Turner, Mary Grant Bruce (qq.v.) and children's literature), Australian History (Georgiana McCrae (q.v.) and the Boyd family) and American Literature (in particular Edith Wharton).
In 2004 Dr Niall was made an Officer of the Order of Australia to acknowledge her services to Australian Literature. In October 2005 Monash University awarded her the Honorary Degree of Doctor of Letters.
Dr Niall is the sister of Frances O'Neill and aunt of Kate Ryan and Jake Niall.