O'Neil was an historical genre painter who worked primarily with historical and literary subjects, but his best-known paintings dealt with the Indian Mutiny. Eastward, Ho! August 1857 depicts the British troops embarking for India, and a second painting, Home Again, (1859) shows the troops returning to England.
He was a member of The Clique, a group of artists in the 1840's who, like the later Pre-Raphaelite Brotherhood, met regularly to discuss and criticize one another's works. The other members of The Clique were William Frith, Augustus Egg, John Phillip and Richard Dadd.