The Union of Great Britain and Ireland came into effect on 1 January 1801. In future Ireland would have one hundred MPs in the British house of commons, as well as twenty-eight elected peers and four Protestant bishops in the house of lords. Catholics were still prevented from sitting in parliament, and indeed were excluded from many public offices. Comwallis, as lord lieutenant, had pressed for Catholic emancipation to be included in the terms of the Union which the two parliaments were asked to agree. However, the British prime minister, William Pitt, was persuaded that this might be unacceptable to the Protestant MPs in Dublin.

Pitt believed that emancipation would make the Union acceptable to Irish Catholics and planned to put the necessary legislation before the enlarged Westminster parliament.  The Catholic hierarchy in Ireland consequently supported the Union. However, there were many opponents at Westminster, in addition to most of the new Irish MPs. More important, King George III was implacably hostile to emancipation. When Pitt found his own cabinet divided on the issue, he resigned in February 1801.

In the aftermath of the 1798 rising, the issue of emancipation was not of great consequence to the mass of Catholics. However, the Catholic hierarchy and upper classes, as well as the growing numbers of Catholics in commerce and the professions, felt some sense of betrayal. The issue continued to receive attention at Westminster, where Henry Grattan made it his principal concern, but a number of reforming measures were rejected.

The turning point came in 1823, when Daniel O'Connell founded the Catholic Association.   O'Connell, bom into a prosperous Catholic family in County Kerry, had been educated in France until forced out by revolutionaries. In Ireland, where he became a successful barrister, he was critical of the 1798 rising and of the agrarian violence perpetrated by secret societies such as the Whiteboys and Ribbonmen. By pursuing peaceful methods, and by mobilising Catholic smallholders and workers in mass demonstrations, he came to dominate Irish politics for two decades.

The Catholic Association sought not only to remove what remained of the penal laws, but also to further Catholics' interests at a time when many were suffering from economic depression and from unsympathetic landlords. When an annual membership fee of one guinea proved unpopular, O'Connell introduced a "Catholic rent" of one penny per month, and numbers soared as the money was collected by parish priests. Although opposed to violence, O'Connell never hesitated to speak aggressively in depicting Catholic grievances. The government responded, first by trying to prosecute him, then by banning the association, but O'Connell was undeterred.

At the 1826 general election, pro-emancipation candidates won several seats. The most notable success was in County Waterford, where O'Connell's oratory roused the so-called "forty shilling freeholders" to vote against a member of the powerful Beresford family, who owned much of the county. In 1828, O'Connell himself won a by-election in County Clare. Unable to swear the oath of supremacy, O'Connell could not take his seat, but the victory persuaded the government led by the Duke of Wellington that emancipation must be granted.

King George IV reluctantly yielded, and early in 1829 a Catholic Relief Bill received royal assent. Henceforth Catholics could sit in parliament without taking the oath of supremacy, and almost every office was open to them. However, the forty-shillings franchise was raised to ten pounds, so that many of O'Connell's supporters immediately lost their vote. O'Connell became an influential MP at Westminster, but failed in his second major campaign. In 1840 he formed an association to press for repeal of the Union, but lost authority after he yielded to a government ban on a proposed mass meeting at Clontarf in 1843.