McNabb was born in Portaferry, County Down, Ireland, the tenth of eleven children. He was educated during his schooldays at the diocesan seminary of St. Malachy's College, Belfast. On 10 November 1885 he joined the novitiate of the English Dominicans at Woodchester in Gloucestershire, England and was ordained in 1891. After studies at the University of Louvain (where he obtained in 1894 the degree of lector in Sacred Theology), he was sent to England where he served for the remainder of his life.

Fr. McNabb was a member of the Dominican order for 58 years and served as professor of philosophy at Hawkesyard Priory, prior at Woodchester, parish priest at St. Dominic's Priory, and prior and librarian at Holy Cross Priory, Leicester, as well as in various other official capacities for his Dominican province. Between 1929 and 1934, he lectured on the Summa Theologica of St. Thomas Aquinas under the auspices of the University of London External Lectures scheme. Tens of thousands of people heard him preach in Hyde Park, where he did not shy away from taking on all challengers ... Protestants, atheists, and freethinkers ... before vast crowds every Sunday, or heard him debate such luminaries as George Bernard Shaw in the city's theaters and conference halls on the burning social issues of the day.

Fr. McNabb was described as a 13th-century monk living in 20th-century London, pursuing such tasks as reading the Old Testament (and taking notes on it) in Hebrew, reading the New Testament (and quoting from it) in Greek, and reading the works of St. Thomas Aquinas (and writing his reflections on them) in Latin. Throughout his life, Fr. McNabb had little to call his own, except his Bible, his breviary, and his copy of the Summa Theologica.

Fr. McNabb was among the early Catholic ecumenists, seeking in particular to promote reunion between the Catholic Church and the Anglicans. Towards the end of his life, he wrote, "God knows how much I have striven and prayed to mend the shattered unity of Christendom." As a young priest, he came under the influence of the convert bishop of Clifton, William Robert Brownlow, who, after his reception into the Catholic Church by Newman, not only kept many Anglican friendships but made others among Nonconformists. Brownlow was the author of a work breathing a strong ecumenical spirit titled Catholics and Nonconformists: or Dialogues on Conversion (1898). McNabb regarded him as one of his "masters and heroes" and wrote his biography. While prior at Woodchester, McNabb was in correspondence with Anglicans on both sides of the Atlantic. He was host to his Cotswolds neighbour, the Rev. Spencer Jones, rector of Moreton-in-Marsh, leading Anglo-Catholic and author of England and the Holy See: An Essay Towards Reunion (1902). He also contributed to the early issues of The Lamp, a paper edited by Fr. Paul Wattson, who, after becoming a Catholic, was to promote the Unity Octave through it for almost half a century. McNabb's lifelong interest in ecumenism culminated in his book The Church and Reunion (1937), published six years before his death.

McNabb sought also to promote a vision of social justice inspired by St. Thomas and by Pope Leo XIII's Rerum Novarum, which called upon "every minister of holy religionto bring to the struggle [for a broad distribution of property] the full energy of his mind and all his powers of endurance", as well as to shore up both faith and reason against the perceived threat of modernism.

He died at St. Dominic's Parish, London and was buried in St. Mary's Roman Catholic Cemetery, Kensal Green, London.