After training under his father, a local schoolmaster, Spruce began a career as a tutor and then as a mathematics master at St Peter's School in York between 1839 and 1844.
In 1844 his paper on "The Musci and Hepaticae of Teesdale",[4] the result of a three-week excursion, showed his skill at locating and identifying rare species.
[5] Spruce came to the attention of William Jackson Hooker, the director of the Royal Botanic Gardens at Kew, and was recommended for a collecting expedition to the Pyrenees, which he undertook in 1845–1846.
Spruce issued exsiccata-like series, among others the work Musci Pyrenaici, quos in Pyrenaeis centralibus occidentalibusque, nec non in agro Syrtico, A. D. 1845-6.
Both subsequently well known for their work on natural selection, Wallace and Bates traveled along the tributaries of the Amazon, occasionally crossing paths with and sharing information with Spruce.
Within the first two years of his expedition, Spruce had trekked along the full length of the river Trombetas to British Guiana, crossing over the Rio Negro to Manaos.
[9] Towards the end of his expedition through South America, Spruce studied indigenous cultivation of cinchona in the Andes of Peru, then successfully exported seeds and young plants as requested by the government of India.