Anne and John Hunter's engagement dragged on. John started to work with a fashionable dentist James Spence, and after a while he began to acquire patients and pupils of his own. His prospects were looking good, especially when he was elected a Fellow of the Royal Society in 1767 and appointed a surgeon at St George's Hospital in 1768. In the meanwhile an added complication had arisen: although much argued about by his many biographers there is little doubt that in his experimental zeal John injected himself with venereal disease in 1767, recording its progress with chillingly meticulous, clinical accuracy—not a propitious basis for marriage. However, although his health was arguably permanently affected, after about three years he felt himself to be cured. He continued to make frequent visits to the Home household and finally, with the acquisition of his brother's house at 42 Jermyn Street in 1769, and the publication of his first book, The Natural History of the Human Teeth in 1771, John Hunter, now aged 43 and Anne Home aged 29 were able to marry. The wedding took place at St James's Piccadilly at 8am on 23 July 1771, witnessed by Anne's parents. William was not invited, John having written to him the previous day: ‘Dear Brother: Tomorrow at eight o'clock and at St James's Church, I enter the Holy State of Matrimony. As that is a ceremony which you are not particularly fond of, I will not make a point of having your company there […] Married or not married, Ever yours, John Hunter’.

The newly-weds spent their honeymoon at Earl's Court, in the country house that John had acquired before going into the Army. Now part of south-west London, Earl's Court was then a village surrounded by market gardens. The house had a large garden and many outbuildings and he used it as a retreat from his day-to-day surgical practice and as a place where he could observe as well as experiment on living animals and carry out research into cross-breeding. As well as the usual farm animals, he began to collect exotic mammals and birds, some purchased from dealers, others begged from friends and acquaintances returning from abroad.