Elisha, a Methodist minister, became an entrepreneur in irrigation, real estate and dried fruits in Mildura. Elizabeth was a bush nurse and midwife.
 
The twins attended Methodist Ladies College, Melbourne, where Mary De Garis was Dux in 1898. The 31st woman to enrol in medicine, she began medical training in 1900 at the University of Melbourne. The medical women mentored each other; De Garis helped form the Victorian Women's Medical Students' Society. She graduated in 1905 and in 1907 was the second woman in Victoria to obtain a Doctorate of Medicine.

With excellent results she obtained a Resident position at the Melbourne Hospital. After this year, in 1907, she travelled to Muttaburra Hospital, Queensland, where she was the sole surgeon for fourteen months. She then sailed to the UK, Europe and the USA to complete postgraduate courses, returning to Melbourne in 1910.
 
In September 1918, on her mother's death, De Garis resigned and returned to Melbourne, arriving in February 1919.By April 1919 she was practising as Geelong's first female medical practitioner. Here she lobbied for better female medical care, achieving success in having women elected to the hospital general committee (1925), the building of its first maternity ward (1924) and the establishment of its ante (1927) and postnatal (1932) clinics. When the maternity ward was commissioned in 1931, De Garis was appointed head of the unit. At a time of high maternal and infant death rates her record of 1,000 deliveries completed by 1938 without the loss of a mother was outstanding. In 1941 she became the honorary consultant to the Maternity Ward.

She practised until her late seventies, well known in Geelong and Melbourne with a grateful female clientele.

In 1954 a house in the grounds of the Geelong Hospital was named De Garis House in her honour.