Leyland was apprenticed to Liverpool's oldest independent shipping line, John Bibby & Sons, in 1844. He was promoted several times until be was appointed a merchant in the firm in 1859. He proved himself in 1861 by settling a dispute between the firm and the Birkenhead corporation and was made a partner as a result. Leyland bought out his employers and changed the company name to his own in 1871. The Leyland Line expanded into transatlantic trade and by 1882 comprised some 25 steamships. His son, Frederick Dawson Leyland, took over from his father when he retired in 1888.
The business man was married to Frances, née Dawson (1836–1910). They lived with their four children in Falkner Square in Liverpool until 1867 when they leased Speke Hall, just outside the city. They lived there until 1877, when they moved to the nearby Woolton Hall.
Leyland was a passionate supporter of the arts and he was close friends with the artist Dante Gabriel Rossetti (1828 - 1882) and the Liverpool collector John Miller. He also had a close relationship to the American artist Jame McNeill Whistler (1834 - 1903) until they famously fell out in the late 1860s, as well as Edward Burne-Jones (1833 - 1898). His grave in Brompton cemetery, London, is marked by a bronze monument designed by Burne-Jones.