Born in England in 1835, and educated in London, where he received a classical and literary education, Giles emigrated when he was 15 years old and joined his family in Adelaide. They had come to Australia the previous year. He spent some time working on cattle and sheep stations along the upper Darling River during which time he became a competent bushman.

Between 1872 and 1876 he led 5 expeditions into Australia's unknown western interior, the last 2 on camels. He was driven by a desire to be the first to penetrate the area and set out without official support. He was never given material reward for his exploration work, but was awarded the gold medal of the Royal Geographical Society.

During his travels he discovered Mount Olga, named the Gibson Desert and crossed the continent from east to west and later went back again by a different route. Despite initial setbacks and seemingly impenetrable wilderness, Giles never weakened in his purpose or his love of exploration. At one point in his travels, he sent his companion, Gibson, on to fetch help, riding their last horse, then struggled along on foot. Gibson was never heard of again. Giles ate the last of his horsemeat and rapidly became weaker. Hunger drove him to eat, whilst still alive, a small dying wallaby, whose mother had evidently thrown it from her pouch. He was so hungry he wished he had its mother and father to "serve in the same way."

In 1897 he died after contracting pneumonia whilst working as a clerk in the Coolgardie gold fields. Giles styled himself as "the last of the Australian explorers."