Admitted Sizar at St John's College in 1832, Colenso gained his BA as Smith's Prizeman and 2nd Wrangler in 1836. He was admitted a Fellow of St John's in 1837 and worked as a tutor from 1842 to 1846. During this time he wrote school treatises on arithmetic and algebra which were very well received. He served as vicar of Forncett St Mary in Norfolk until 1853 when he was appointed Bishop of Natal. In South Africa he devoted much of his time to the education of the Zulus and devised a written Zulu grammar, in which he printed many books including a Zulu-English dictionary and a translation of the New Testament. His discussions with the natives on religious matters provoked serious reservations about church teachings and led him to write 'Commentary on St Paul's Epistle to the Romans' in 1861 and a 'Critical Examination of the Pentateuch' between 1862 and 1879. These caused much controversy amongst the church fraternity, both in England and in South Africa, and he was formally deposed and excommunicated by Dr Gray, Metropolitan Bishop of Capetown, in 1863. This ruling was overturned by the Law Courts in England and, though the South African church did all it could to undermine him, Colenso retained his position as Bishop of Natal, maintaining much support from the local population.
Colenso's popularity was severely undermined, however, by the stand he took during the rise of troubles between the colonists and the native African population in the 1870s. His support of the Amahlubi tribe and his championing of their chief Langalibalele, who had been tried and sentenced to death in 1874, led to the Matshana enquiry which exposed both the corruption of some Colonial officials and much underhand dealings towards the natives. Colenso's outspoken stance aroused bitter feelings in the colony, which were further exacerbated by his support for the Zulu king Cetshwayo and his opposition to the invasion of Zululand in 1878 and the subsequent war. He continued to fight for the restoration of Cetshwayo and for Zulu rights, despite his failing health, until his death in Pietermaritzburg in 1883.
He married Sarah Frances Bunyon in 1846 and had five children (three girls and two boys).
Correspondence of JWC discussing theological matters and details of his church work and life in Natal; a notebook containing copies of letters sent to JWC on theological matters; correspondence arising from the visit of the Reverend James D La Touche to Natal in support of the work of JWC.