Samuel Leigh was born probably on 1 September 1785 at Milton, Staffordshire, England, the son of Matthew Leigh, an engineer; his mother's name is unknown. Samuel initially belonged to the Congregational church, but later joined the Wesleyans. After two years at Dr David Bogue's Congregational seminary at Gosport, Hampshire, he withdrew and offered himself for Wesleyan missionary work. After being appointed to Montreal, Canada, in 1814, Leigh was ordained, but as war seemed imminent in North America he was diverted to Australia. Arriving there in 1815 as the first Wesleyan missionary, he travelled extensively, laying the foundations of Methodism at Sydney, Castlereagh, Windsor, Liverpool and Richmond. He was also instrumental in establishing the Sydney Asylum for the Poor and the Colonial Auxiliary Bible Society.
Leigh became a close friend of Samuel Marsden, chaplain of New South Wales, who enabled him to visit New Zealand during May and June 1819 in order to recuperate from a breakdown in health. He mediated in a dispute among the members of the Church Missionary Society in the Bay of Islands, and recommended that their work should be organised as circuits, on the Wesleyan model. On this visit Leigh conceived the idea of a Wesleyan mission to the Maori. Returning to England in 1820, he persuaded the conference to authorise the canvassing of the industrial areas for goods to be used in barter. While in England, he married Catherine Clowes at Hanley, Staffordshire, on 14 December 1820. The couple sailed for Sydney, and from there to the Bay of Islands. Arriving on 22 January 1822, they were given hospitality by William and Dinah Hall of the CMS, and lived with them for 16 months. After the arrival of William White in May 1823, he and Leigh established the Wesleydale mission at Kaeo, near Whangaroa Harbour.
Once again Leigh's health broke down and after the arrival of John Hobbs and Nathaniel Turner he left Kaeo on 19 August 1823. The Leighs and Marsden embarked on the Brampton from the Bay of Islands on 7 September 1823; the ship was wrecked on a reef, the passengers rescued, and the voyage resumed on 14 November. After recuperating in Sydney, Leigh continued his Australian ministry until 1831. Catherine Leigh died in May that year, and Leigh returned to England, devoting himself to circuit ministry. On 16 August 1842 at Gillingham, Dorset, he married Elizabeth Kaye, a widow; they adopted two children. Leigh retired to Reading in 1845, where he died on 2 May 1852 from the results of a stroke suffered while advocating the missionary cause.
Although Leigh's residence in New Zealand was short and he had little facility in the Maori language, the commencement of the Wesleyan mission in New Zealand was due to his determined advocacy. His friendship with Marsden, and his belief that the agents of the Church and the Wesleyan Missionary societies could work together to their mutual advantage, meant that Leigh was able to assist Marsden during the troubles with Thomas Kendall and to help the CMS lay missionaries clarify their goals in 1819. This mutual trust and co-operation between the two missions continued until the early 1840s when the influence of the Tractarian movement began to heighten denominational differences in New Zealand.