Nerli was born in Siena in 1860. His father was an Italian aristocrat, and perhaps it was from him that Girolamo inherited the style and flair for which he later became famous. The young Girolamo went to Florence to study art, and there he encountered a group of Italian artists called the Macchiaioli, who were reacting against the formal rules of art of the time. Inspired by them, he brought a distinctly different approach to painting, first to Australia, then to New Zealand.

Nerli was a flamboyant individual as well as an unconventional painter, and his three years in Dunedin helped to make the city the art centre of the country. He was elected to the council of the Otago Art Society, and in 1894 was one of a group of three artists who opened the Otago Art Academy. He was a charismatic teacher, and his private classes were so popular that the Dunedin School of Art and Design decided to employ him as a teacher of painting. It was clearly better to hire him than compete with him.

Nerli encouraged his students to look beyond the limitations of New Zealand art to the innovativeness of Europe. Among these students was Frances Hodgkins, who later became one of New Zealand's most famous expatriate artists. In 1896, Nerli suddenly moved to Auckland where he opened a studio and exhibited his work. In 1898, he married Marie Cecilia Josephine Barron, and immediately after their marriage the couple sailed for Australia. They never returned to New Zealand, although from time to time Nerli sent back paintings for exhibition. Eventually, he went back to Europe with Marie. The last years of his life were a struggle with poverty as he tried to rebuild his declining reputation. He died in Italy in 1926.