While he was still a child, the family moved to Wexford, where he received an informal education. In 1842, McGee left Ireland and travelled to North America where he joined the staff of the Boston Pilot, a Catholic newspaper. Two years later, at the age of 19, he was editor of the paper, using his position to lobby for Irish independence and the rights of Irish Catholic immigrants. He also supported the American annexation of Canada.

In 1845 McGee returned to Ireland to work at the Freeman's Journal, and later the Nation. He married Mary Teresa Caffrey at Dublin on July 13, 1847. He became involved in the Young Ireland movement and the Irish rebellion of 1848, which failed. He was forced to flee to the United States, where he continued to edit newspapers (including his own, the Nation), agitate for Irish independence, and devise projects for the betterment of Irish immigrants. When McGee's projects failed to gain support, he moved to Montréal in 1857 at the invitation of the local Irish community.

McGee's attitudes toward Canada had changed by the time he came to Montréal. He no longer supported American annexation, and in fact he urged new Irish immigrants to choose Canada over the United States. In Montréal, McGee became editor of the New Era, which he used to discuss Irish politics and the future of Canada.

McGee's work at the New Era was a springboard for his start in Canadian politics. In December of 1857, he was elected to the Legislative Assembly of the Province of Canada. He sat with the Reform government in 1858, following it into opposition when George Brown was defeated in 1861. Over the next several years, McGee tried various means of giving the reformers a wider base of support. He joined the Cabinet in 1862, and chaired that year's Railway conference at Québec City. When the railway plan fell through, McGee was dropped from Cabinet. He eventually broke with the reformers in favour of the Conservatives. When the Conservatives gained power in 1863, McGee became the minister of agriculture, immigration and statistics.

McGee was an early visionary of Confederation. In the pages of the New Era, he called for the construction of a new nationality through the unification of British North America. He also lobbied for the construction of a railroad, and for the creation of a province for Aboriginal peoples. In 1860, he said, "I see in the not remote distance one great nationality bound like the shield of Achilles, by the blue rim of ocean ... I see within the ground of that shield the peaks of the western mountains and the crests of the eastern waves." In 1864, McGee helped to organize the Canadian Visit, a diplomatic goodwill tour of the Maritimes that served as a prelude to the first Confederation conference. During this tour, McGee delivered many speeches in support of union and lived up to his reputation as the most talented political orator of the era. He was a delegate to two Conferences , the Charlotte and the Quebec. In 1865 he delivered two speeches on the union of the provinces, which were subsequently bound and published.

As he grew older, McGee became vehemently opposed to Irish Republicanism. His outspoken criticism of the Irish independence movement and the Fenians alienated large sections of the Irish community, in Canada and elsewhere.  McGee also had a complex relationship with the Catholic Church.  Anti-clerical in his youth, he became passionately devout in his later years.

By 1866, his political star was fading.  He was not invited to the Conference in London of that year. While he was elected to the House of Commons in 1867 by a slim majority, he was not included in Macdonald's first post-Confederation Cabinet. By 1868, McGee was planning to leave politics for a job in the civil service. He also hoped to spend more time on his writing and poetry. However, he was not given the chance.  On April 7, 1868, McGee attended a late-night session in the House of Commons, where he gave a passionate speech in favour of national unity. Returning home, he was shot and killed as he entered the door of his rooming house on Sparks Street in Ottawa. It is generally believed that McGee was the victim of a Fenian plot. However, Patrick James Whelan, who was convicted and hanged for the crime, was never accused of being a Fenian by the Crown prosecutor.

McGee was given a state funeral.

There follows shortly two small examples of his poetry.