He campaigned for Catholic Emancipation, that is, the repeal of all anti-catholic legislation enforced in Ireland. As part of his campaign, he sought and won election to the House of Commons in 1828, even though as a catholic, he was ineligible for membership because of his inability to take an oath to the Queen as head of the Church of England. His election and subsequent re-election in 1829, forced the government of the Duke of Wellington in 1829 to repeal the prohibitions and grant emancipation, which also liberated not just Catholics but Presbyterians and all faiths other than the established Church of Ireland.
O'Connell also campaigned for Repeal, that is, repeal of the Act of Union that in 1801 merged the Kingdom of Great Britain and the Kingdom of Ireland to form the United Kingdom of Great Britain and Ireland. He argued for the re-creation of an independent Kingdom of Ireland to govern itself, with Queen Victoria as Queen of Ireland. To push this, he held a series of Monster Meetings (mass rallies) throughout Ireland. Though Charles Stewart Parnell (who dominated Irish politics in the last quarter of the nineteenth century) is more usually associated with the title, O'Connell was popularly described as the Uncrowned King of Ireland. His campaign for Repeal was unsuccessful.
He died in 1847 while travelling to Rome. He is buried in Glasnevin Cemetery in Dublin. His sons all served in Parliament.
The principal street in the centre of Dublin, previously called Sackville Street, was renamed O'Connell Street in his honour in the early twentieth century. His statue (made by the sculptor who designed the Prince Albert Monument in London) stands at one end of the street, with a statue of Parnell at the other.