Guy Griffiths was always called by his second name. He was born on 18 July 1876, the son of George Neville Griffiths, who was a grazier with property in New South Wales and Queensland. He was educated at the Cooerwull Academy and the Sydney Grammar School.

In 1896 he entered the faculty of arts at Sydney University and won the George Allen Scholarship in mathematics. In 1897, he entered the faculty of medicine, but continued his mathematical studies as an evening student. He graduated as bachelor of arts with honours in 1898. He was a resident at St Andrew's College, and represented the College in running, rowing, cricket, tennis and football. He took an active part in university life, being on the editorial committee of Hermes, president of the Undergraduate Association in 1899 and president of the Medical Society in 1901.

He graduated MB in 1900. In 1911, he was admitted to the degree of doctor of medicine, his thesis being on the use of tuberculin in diagnosis and treatment. In the same year, he took the degree of master of surgery. In 1948, he proceeded to the degree of master of arts. In 1938 he became a foundation Fellow of The Royal Australasian College of Physicians.

He was a resident medical officer at Sydney Hospital in 1901 and in the following year, served as resident pathologist under Sydney Jamieson. After leaving the hospital, he went into general practice at Gundagai, returning to Sydney in 1904 to practise as a physician.

His main appointments were at the Royal North Shore Hospital of Sydney. In 1909, he was appointed honorary pathologist and anaesthetist. In 1911 he was appointed honorary medical officer and, in 1919, honorary physician, and retained this appointment until his retirement in 1937. From 1927 to 1933 and again in 1935, he was medical representative on the Hospital Committee. In 1941, he was appointed honorary consulting physician.

His chief medical interest was tuberculosis. At one time, he was honorary physician to the Anti-Tuberculosis Association of New South Wales and honorary examining physician, Queen Victoria Home for Consumptives. In 1912, he was a member of the New South Wales Government Tuberculosis Advisory Board. In 1917, he enlisted in the AIF and saw service in the Middle East, attaining the rank of major.

In 1902, he married Miss Elizabeth Deane, having two sons and three daughters. When Guy Griffiths entered North Shore Hospital, he always used to bow to a marble tablet in the front hall upon which the name of his brother, killed at Lone Pine, was inscribed on a list of benefactors. This semi-weekly rite often surprised those who witnessed it for the first time. To those who joined the College after the Second World War, he is remembered as a tall, lone, bearded figure who always sat in front seat at College meetings in the old Stawell Hall. His appearance and bearing were such as to initiate enquiries as to who he was.