Ordained in 1816, Keble was educated at the University of Oxford and served as a tutor there from 1818 to 1823, when he left to assist in his father's parish. In 1827 he published The Christian Year, a volume of poems for Sundays and festivals of the church year. Widely circulated, the book did more than any other to promulgate the ideas of the High Church movement in Anglicanism.

Keble was professor of poetry at Oxford from 1831 to 1841. By 1833, however, he had become known as a leader of the Oxford Movement, which was generally considered to have been initiated by his sermon “National Apostasy,” given that year on July 14 at the university chapel. Centred at Oxford, the movement sought at first to respond to government efforts to appropriate church funds and property but gradually expanded its activities to a more general theological and pastoral agenda. Keble wrote 9 of the Oxford Movement's 90 Tracts for the Times, which were intended to rouse the Anglican clergy against the theory of a state-controlled church and which caused the movement's advocates to be known as Tractarians. The Tractarians encouraged study of the early Church Fathers, edited their works, and arranged for their translation. When John Henry Newman's conversion to Roman Catholicism in 1845 threatened the continuation of the Oxford Movement, Keble and E.B. Pusey (Pusey, E B) managed by their persistence to keep the movement alive.

Keble, who served as a country vicar at Hursley from 1836 until his death, is remembered as much for his lyrics as for his Tractarian role. Among his books of verse are included The Psalter or Psalms of David (1839) and the poems for childhood, Lyra Innocentium (1846); he also wrote numerous hymn lyrics, including “O God of mercy, God of might.” In 1869 Keble College, Oxford, was founded in his honour.