Born near Zorra, Oxford County, Ontario, Canada, Mackay was christened by William Chalmers Burns, an English Presbyterian missionary to China, whose example inspired the younger man to become a missionary also. A graduate of Princeton Theological Seminary, Mackay arrived in Taiwan in 1872 as the first foreign missionary of the western division of the Presbyterian Church in Canada. After consulting English Presbyterian missionaries already working in southern Taiwan, Mackay decided to establish his mission in the north with its headquarters at Tamsui (Danshui).
He indefatigably conducted Christian work not only among the Chinese but also among the aboriginal populations. In his evangelistic work, he was greatly assisted by his Chinese wife, Tui Chang Mia (Minnie Mackay), and by A. Hoa, his first convert and lifelong disciple. Mackay was a missionary entrepreneur skilled at raising funds to build churches and to found schools, the most important of which were Oxford College in Tamsui and a theological school that became Taiwan Theological College near Taipei. The Taiwanese referred to him as the Black-Bearded Barbarian of Formosa. He received an honorary D.D. from Queen's University in Kingston, Ontario, and his name is perpetuated by the Mackay Memorial hospital in Taipei.