Ordained in 1852, Liddon became vice principal at the new seminary at Cuddesdon, Oxfordshire, in 1854, and he was made vice principal at St. Edmund Hall, Oxford, in 1859. He used his post at Oxford to maintain and advance the movement, which had suffered a setback after the conversion in 1845 of its chief figure, John Henry Newman (Newman, John Henry), to Roman Catholicism. In 1864 Liddon became chaplain to W.K. Hamilton, bishop of Salisbury and one of the few bishops then favourable to the Oxford movement's renewal of Roman Catholic principles within the Anglican church. His stature as a spokesman was enhanced by his Bampton lectures of 1866, published the following year as The Divinity of Our Lord and Saviour Jesus Christ.

In 1870 Liddon became a canon of St. Paul's, London, and Ireland Professor of Exegesis at Oxford. His sermons at St. Paul's attracted vast congregations for the next 20 years. Like others in the movement, he consistently opposed preferment (the ecclesiastical system of promotions) and is known to have refused at least two bishoprics. His concern with Christian unity prompted him to participate in developing the Old Catholic movement after the Vatican Council (Vatican Council, First) of 1869–70, and he traveled in Russia and the Middle East, contacting Orthodox church leaders.

As an associate and admirer of Pusey at Oxford, he favoured Pusey's attitudes, in contrast to those of younger thinkers in the movement; after Pusey's death in 1882, Liddon began his authorized biography, published posthumously as Life of Edward Bouverie Pusey (1893–97).