He was called to the Irish Bar in 1805 and practised with great success on the home circuit. Blackburne was nominated a King's Counsel in 1822 and administered the Insurrection Act in Limerick for two years, effectually restoring order in the district. In 1826 he became the King's Third Serjeant-at-law and in 1830 was advanced to the Second Serjeant. A year later, he was appointed Attorney-General for Ireland in the Whig administration of Earl Grey 'though known to be a tory... with a view to the Irish administration having a broad political base' and on this occasion was sworn of the Privy Council of Ireland. He held the post as Attorney-General until 1834; he was readmitted in 1841 and after serving for a year, became Master of the Rolls in Ireland. As Attorney General he clashed with Daniel O'Connell when he insisted, against O'Connell's wishes, on the appointment of Abraham Brewster as Law Adviser to the Lord Lieutenant of Ireland. Blackburne's statement that he "would not tolerate a refusal to ratify the appointment", is an indication of the influence which could then be wielded by a strong Attorney General. In 1845, he was chosen Chief Justice of the Court of Queen's Bench. Blackburne was appointed Lord Chancellor of Ireland in February 1852, but was replaced in October. After a break of four years, he became a Lord Justice of Appeal. In 1858 'he was invited by Lord Derby again to become lord chancellor, but he declined on account of his advanced age and failing health. He changed his mind, however, and decided to accept Derby's offer but was told that the position had been offered to and accepted by Joseph Napier.' He was bitterly disappointed, referring to the decision as "a harsh and cruel blow". In 1866, he began a second term as Lord Chancellor, which ended with his death in the next year. Blackburne prosecuted Daniel O'Connell and presided at the trial of William Smith O'Brien. From 1851, he was vice-chancellor of the University of Dublin. A devoted member of the Church of Ireland, he opposed any measure hostile to its interests, arguing that an attack on the Church. was an attack on the Union itself.
Family
In 1809, he married Jane, daughter of William Martley of Ballyfallen, Co. Meath and his wife Elizabeth, daughter of Richard Rothwell of Berford, Co. Meath. They were the parents of three sons and three daughters. Blackburne bought Rathfarnham Castle in 1852, where his family continued to reside for three generations.