Born in Saint Petersburg, O’Neil moved to England with his family at the age of six. In 1836 he entered the Royal Academy Schools and began exhibiting at the RA from 1838. With Richard Dadd and W. P. Frith, he became a member of the ‘Clique', a group of young artists based in St John's Wood, dissatisfied with the traditionalist methods of the Academy.
He was a successful and prolific painter, at ease in most fields, including portraiture, landscape and history but is chiefly remembered for his hugely successful genre scenes, in particular Eastward Ho of 1857. Emotionally-charged and meticulously detailed, it shows the wives, sweethearts, and families of troops embarking an army ship at the time of the Indian Mutiny. His equally popular paintings Home Again and Princess Alexandra Landing at Gravesend were in a similar vein. He exhibited at the Royal Academy until 1879 and at the British Institution for 22 years from 1839. He was elected Associate of the Royal Academy in 1879 and died in London the following year.