George O'Brien is said to have been born at Dromoland Castle, County Clare, Ireland, and was baptised in the parish of Kilnasoolagh (Newmarket-on-Fergus) on 16 September 1821. He was the fifth son of nine children of Captain (later Rear Admiral) Robert O'Brien and his wife, Anne O'Brien, who were first cousins. O'Brien's schooling and early career remain obscure. There is an unsubstantiated report of study in Germany; the belief that he was educated at Rugby and Oxford has been disproved. The titles of some of his pictures imply travel in England and Egypt, but there is no confirmation of this.
In 1850 the arrival in Melbourne of an unassisted immigrant, G. O'Brien, on the Midlothian, is recorded. A year later a G. O'Brien was appointed a draughtsman in the surveyor general's office, and from that time the record of his life is more certain. On 23 February 1853 he married Jane Mashford at St James's Church, Melbourne, Australia. Although the births of only six children are recorded, family tradition claims there were seven children. He was practising as an architect between 1854 and 1858; he became a committee member of the Victorian Fine Arts Society in 1853, and an exhibitor of paintings in Melbourne from 1853 to 1858. Although the date of O'Brien's departure for New Zealand is unknown, watercolours of Australian subjects imply that he was still living in Melbourne in 1863.
O'Brien's name first appears on the Dunedin ratepayers' roll on 3 December 1863; he lived in Dunedin until his death. He was employed erratically by the Dunedin Town Board in 1864 and 1865. In 1867 he advertised for art pupils, and tried his hand at lithography in 1868. Between 1872 and 1879 he was employed, apparently without interruption, as assistant city surveyor by the Dunedin City Council. He prepared perspective drawings for several architects, including William Mason, R. A. Lawson, and W. H. Clayton. On at least two occasions in 1875 and 1878 he did architectural work. He travelled around Otago and Southland and is known to have journeyed to Auckland in 1885–86.
Watercolours by O'Brien were seen in three of New Zealand's earliest major art exhibitions, at Dunedin in 1865 and 1869 and Christchurch in 1870. In 1876 he was a foundation member and a foundation councillor of the Otago Art Society, showing 28 of his own works in the society's first exhibition in the same year. He exhibited only three more times with the society. His work, however, was occasionally seen in Christchurch, Wellington and Auckland.
O'Brien's work as a watercolourist is characterised by the crisp draughtsmanship one would expect from an architect-surveyor, frequently high foregrounds painted with dense, bright colour, and fading to delicate washes in the background. He used conventional framing devices inherited from the landscapes of Claude Lorrain. His finished pencil drawings are minutely crafted, with an attention to detail not universally appreciated.
O'Brien was the only major New Zealand artist of his generation to take townscape, set within a broader landscape setting, as an important theme. In the 1880s there was a change in public taste, and O'Brien's work reflected this change. The atmospheric romanticism of John Gully and William Mathew Hodgkins was now dominant, and it replaced in popularity the precise topographical manner of J. B. C. Hoyte and O'Brien. In the more conventional, picturesque subjects he now chose, O'Brien's achievement fell short of that seen in earlier works. Nevertheless, late views of Auckland and Dunedin demonstrate that his skill survived undiminished within the urban context. His work is to be found in the Hocken Library, in Dunedin, the Dunedin Public Art Gallery, the Otago Early Settlers Museum, the National Art Gallery and the Auckland City Art Gallery.
George O'Brien was 'a big man, enormously stout'. He weighed 18 stone and was known to be a heavy drinker. Ill health, and perhaps estrangement from his surviving children, clouded the last years of his life. On 30 August 1888 he died at the home of Henry and Mary Anne Divers, friends with whom he had been living. It was to the wife of this couple that he bequeathed all his possessions, valued at less than £20. He was buried in the Northern Cemetery in the same plot as his wife Jane, who had predeceased him.