In 1871 Mackay became the first foreign missionary to be commissioned by the Canada Presbyterian Church (predecessor of both the Presbyterian Church in Canada and the United Church of Canada), arriving in Taiwan on New Year’s Eve, 31 December 1871.

After consulting with Dr. James Laidlaw Maxwell Sr., a medical doctor serving as a Presbyterian Church of England missionary to southern Formosa (1865), Mackay arrived at Tamsui, northern Formosa in 1872, which remained his home until his death in 1901. Starting with an itinerant dentistry practice amongst the lowland aborigines, he later established churches, schools and a hospital practicing Western biomedicine. He learned to speak vernacular Taiwanese fluently, and married “Minnie” Tiu (張聰明; Tiuⁿ Chhang-miâ), a Taiwanese woman.

He was described by Rev. William Campbell, a contemporary missionary, as

…a little man, firm and active, of few words, unflinching courage, and one whose sound common sense is equalled only by his earnest devotion to the Master. […] During the first year of his stay at Tamsui, he began an educational and evangelistic training movement among the young men who came about him, and this has been greatly blessed throughout that northern part of the Island.

The churches he planted later became the Northern Synod of the present Presbyterian Church in Taiwan. In 1896, after the 1895 establishment of Japanese colonial rule in Taiwan, Mackay met with the Japanese Governor-General of Formosa, Maresuke Nogi. Some families in Taiwan today, particularly of lowland-aboriginal Kavalan ancestry, trace their surname ‘偕’ (‘Kai’ or ‘Kay’) to their family’s conversion to Christianity by Mackay.

In Canada Mackay was honoured during his two furloughs home by the Canadian Church. In 1880, Queen’s College in Kingston, Ontario awarded him an honorary Doctor of Divinity, presented by Principal George Monro Grant and Chancellor Sandford Fleming. Before departing in 1881, he returned to Oxford County, where monies were raised to start Oxford College in Taiwan; a number of young people in the county were inspired to follow Mackay’s example and entered into missionary service with a number of Christian denominations.

In June 1894, at the General Assembly meeting in St. John, New Brunswick, Mackay was elected Moderator of the Presbyterian Church in Canada, the highest elected position in the church. He spent the following Moderatoral year travelling across Canada, as well as writing From Far Formosa: the island, its people and missions, a missionary ethnography and memoir of his missionary experiences.

In 1894 he spoke out against the head tax imposed on Chinese immigrants to Canada. As moderator of the Presbyterian church, he broke precedent to speak in favor of a resolution opposing this tax, saying it was unjust and racist.

Mackay’s From Far Formosa is considered an important early missionary ethnography of Taiwan and an important contribution to the anthropological understanding of the culture and customs of the people of Taiwan during that period. Mackay himself was as fascinated by the cultures and habitat he found as he was disapproving of native practices he viewed as idolatry. He spoke approvingly of the destruction of art and other artefacts previously regarded as sacred by his newly Christian converts. Of his rustic apartment in an aboriginal village, Mackay wrote:

To that place the cast-off machinery of idolatry was brought, and more than once I dried my clothes before fires made of idolatrous paper, idols, and ancestral tablets. Three men were employed to carry other paraphernalia of idol-worship to the museum in Tamsui.

Mackay was otherwise an enthusiastic collector of cultural artefacts and specimens of local flora and fauna. Many items collected by him are today preserved at the ethnology department of the Royal Ontario Museum (Ontario, Canada) and the Aletheia University Museum (Tamsui, Taiwan).

Although Mackay had suffered from meningitis and malaria, he would die of throat cancer on June 2, 1901 in Tamsui. He was interred near Oxford College (牛津學堂; now Aletheia University) in Tamsui, Taiwan; more specifically, his grave is in a small cemetery in the eastern corner of the Tamkang Middle School campus, where his own son was interred adjacent to him. The major private Christian hospital in downtown Taipei is named Mackay Memorial Hospital, built in 1912 to replace the smaller Mackay Hospital he started in Tamsui in 1882. In recent years Mackay’s life has been celebrated by advocates of a Taiwanese identity and historical understanding that stands distinct from the narratives brought to the island by Japan and China.

On June 30, 2004, a large bust statue of George Leslie Mackay was dedicated outside the Oxford County offices in Woodstock, Ontario. The delegation from Taiwan in attendance included representatives from the Aletheia University and the Presbyterian Church in Taiwan. The event was also attended by representatives of the Presbyterian Church in Canada, the United Church of Canada, local, regional, and national Canadian dignitaries, and a number of Mackay descendants from across North America. One of his grandchildren is Dr. John Ross Mackay.

In November 2006, a Canadian Television documentary was aired titled The Black Bearded Barbarian of Taiwan. It was broadcast in both Mandarin and English on OMNI 2 as part of their Signature Series.

Rohrer states that Mackay, “allowed himself to truly encounter and to be transformed by the people he sought to serve.” He gave the local Christians leadership roles in the churches, giving them perhaps more autonomy and freedom than any other western missionary to China in his period.

In 2008 Taiwan’s government invested in the production of the world’s first-ever Taiwanese/English-language opera based on Mackay’s life. Over a hundred opera singers and production crew from Europe, Asia, and the United States were brought for on the project. Mackay: The Black Bearded Bible Man had its world premier on 27 November 2008, at Taiwan’s National Theater and ran until 30 November.

Mackay: The Black Bearded Bible Man took more than five years to produce. Taiwanese composer Gordon S.W. Chin and librettist Joyce Chiou set out in 2002 to create an opera whose subject was drawn from Taiwanese lore and employed local settings. The large cast featured Thomas Meglioranza (baritone) as George Mackay, Chen Mei-Lin (soprano) as Mackay’s wife Tiuⁿ Chhang-miâ, and Choi Seung-Jin (tenor) as Giâm Chheng-hoâ, Mackay’s first disciple and follower in Taiwan. Chien Wen-Pin, a native of Taipei, conducted the National Symphony Orchestra (Taiwan). Lukas Hemleb directed the stage production.