In 1848, a small group of revolutionaries known as Young Ireland launched an ill-prepared uprising which was quickly quelled. Among them were James Stephens and John O'Mahony, who both sought refuge in Paris, a city which harboured plotters exiled from many countries. In 1853, O'Mahony sailed to America in the hope of encouraging Irish emigrants to support a new rising. Stephens returned to Ireland in 1856, tramping throughout the country to assess the people's mood. On 17 March 1858, he formed in Dublin the secret society which became known as the Irish Republican Brotherhood. Later in the year he sailed to America, where O'Mahony became leader of a new organisation called the Fenian Brotherhood. It took its name from the fian or band of warriors led by the legendary Gaelic hero, Finn Mac Cool, and the name Fenians came to be used for the whole body of revolutionary conspirators.

The Fenian movement, which sought a revolution "sooner or never", quickly attracted thousands of young supporters. When one of the 1848 rebels, Terence Bellew McManus, died in America in 1861, his enormous funeral procession through Cork and Dublin showed how widespread was the sympathy for the Young Ireland ideas which Fenianism now embodied. However, Stephens came in conflict with other nationalist organisations which sought to end the Union by constitutional methods, and the Catholic Church was generally hostile. In 1863 his decision to found a weekly newspaper, the Irish People, was criticised by O'Mahony, who preferred secrecy.

Fenianism was strongly supported by Irish emigrants in America. Many gained military experience in the American Civil War, and when this ended in April 1865 Stephens promised an Irish rising later in the year. However, the government had been alerted by its spies, and in September the Irish People was suppressed. Stephens and his closest associates were arrested, but he escaped from prison and reached America. The government quickly took the offensive, arresting suspects and confiscating arms. Some army units, thought to include Fenian sympathisers, were moved from Ireland.

Stephens had now lost influence, and it was left to civil war veterans, notably Thomas Kelly, to instigate a rising in March 1867. It was no more effective than the 1848 fiasco. Kelly had made his headquarters in England, where Fenianism had strong support among Irish emigrants, and had earlier failed in an attack on Chester Castle to capture arms and ammunition. He and another Fenian were arrested in Manchester on 11 September. A week later, they were rescued while being taken from court to gaol. A police officer was shot dead, and three Fenians were subsequently hanged for his murder. They became known as the Manchester martyrs, and their words from the dock, "God save Ireland", were soon embodied in a popular patriotic ballad.

Other Fenian prisoners were treated more leniently, with death sentences being commuted. However, the execution of the Manchester martyrs, for what was perceived as an accidental killing, aroused great anger among Irish people at home and abroad. Equally, there was a growth of anti-Irish feeling in England, particularly in December 1867, when a number of Londoners were killed or severely injured when a Fenian bomb exploded during a rescue attempt at Clerkenwell prison.

Almost fifty years would pass before the next rising in Ireland, and during this period the main thrust of Irish nationalism was provided by a parliamentary campaign for home rule. However, the Irish Republican Brotherhood preserved the ideal of total separation from Great Britain, and some Fenians were active in new organisations like the Land League and the Gaelic League. Of more immediate importance, though, the Fenian rising had further persuaded some British politicians that the Irish problem called for radical measures. Among them was a future prime minister, William Ewart Gladstone.