Mabel Purefoy FitzGerald was born 3 August 1872, the youngest child of Richard Purefoy FitzGerald and his wife Henrietta Mary, née Chester. Whilst her two brothers pursued navy and academic careers respectively, Mabel FitzGerald, along with her four sisters, was educated at the family home North Hall in Preston Candover, Hampshire, and grew up to live the life of a country lady. After both parents died unexpectedly in 1895 and the eldest brother inherited the family estate, the five FitzGerald sisters moved from Preston Candover to live in Shalstone, Buckinghamshire, with their grandmother Sarah Anna Elizabeth FitzGerald, née Purefoy Jervoise, a 'learned lady' who corresponded with the poet Robert Browning and other literary and intellectual figures of the time.

In 1896 the FitzGerald sisters moved to Oxford to share a house in Crick Road, and Mabel FitzGerald started attending classes in histology, physiology and other pre-medical subjects at the University of Oxford. She did so unofficially, as women were not yet admitted to study for a science degree, but soon impressed her tutors with her thoroughness, dedication and critical spirit. From 1899 she went on to research positions at Oxford with Gustav Mann in histology and with Francis Gotch in neurophysiology/neuroanatomy, and in 1901/1902 worked with Georges Dreyer at the State Serum Institute in Copenhagen on staining methods for bacteria. From 1905 to 1908 FitzGerald worked in Oxford with J.S. Haldane on the physiology of the respiratory system, and with William Osler and James Ritchie on clinical bacteriology and pathology. She then travelled to North America on a Rockefeller fellowship to work with Hideo Naguchi in New York on bacteriology, and with A.B. Macallum in Toronto on gastroenterology, discovering the origin of hydrochloric acid in the gastric tubules.

In 1911 FitzGerald was invited by J.S. Haldane to participate in the subsequently celebrated medical expedition to Pikes Peak, Colorado, to study the effects of altitude on the respiratory system. Whilst the men in the expedition team went up the mountain to set up their laboratory in the summit house and study the acclimatization to altitude in themselves over five weeks, FitzGerald travelled extensively in Colorado to investigate the state of full acclimatization in men and women long resident in remote mining towns at altitudes between 5000 ft and 14,000 ft. Two years later FitzGerald travelled in North Carolina to gather data for lower altitudes and to compare them with the Colorado results. Her observations on The Changes in the Breathing and the Blood at Various High Altitudes and Further Observations on the Changes in the Breathing and the Blood at Various High Altitudes, published 1913 and 1914, are what she became most recognized for. Her findings remain the accepted account today of how PACO2 and haemoglobin vary with altitude in full acclimatization. Alongside her extensive lab and field work, Mabel FitzGerald continued to attend lectures and demonstrations, and by 1910 had completed at least 900 hours of courses in physiology, histology, pathology and chemistry, along with three years of clinical classes with Osler. Still, when she applied to study medicine at Cornell University Medical College she was rejected for not having the necessary qualifications. By 1915, the time of her second application to medical school, this time at New York, she had attended at least another 800 hours of classes, including preparatory school lessons to make up for her lack of formal school education, but again she was rejected.

In summer 1915 FitzGerald returned from the USA to Britain to take up a position as Clinical Pathologist at the Edinburgh Royal Infirmary, deputizing for the male post holder who had gone to war. During her four years in this post, she kept attending medical classes and lectures. In 1920 FitzGerald was appointed Lecturer in Practical Bacteriology at the School of Medicine of the Royal Colleges in Edinburgh, and for years also sat on the Board of Management of the School.

In the mid-1930s, she retired to Oxford to care for her ageing sisters, who, all unmarried, still lived together in their house in Crick Road. For more than two decades, Mabel FitzGerald was almost forgotten by scientists, until her work was rediscovered in the course of the centenary celebrations of her mentor Haldane’s birthday in 1960. But it took until her own hundredth birthday in 1972 before FitzGerald received academic recognition for her scientific work. She was finally awarded an honorary M.A. from Oxford University, and she was made a member of the British Physiological Society, with her papers being quoted for comment in the 1973 Oxford University examinations.

Mabel FitzGerald died of bronchopneumonia at 12 Crick Road, Oxford, on 24 August 1973, and was buried in Shalstone, Buckinghamshire.