His family connections meant he advanced rapidly in the church, becoming vicar-general of the diocese of Waterford and Lismore. He seems to have spent far more time travelling than attending to his duties as a churchman and spent 1733-36 undertaking a series of tours in Europe. From 1737-42 he visited the Near East, visiting Egypt, Jerusalem, Palestine and Greece. These travels were later published in his 'Description of the East' of 1743 and 1745, works which were praised by Edmund Gibbon.
During the years 1747-60, Pococke made a number of tours around various parts of Ireland. The longest of these tours occurred in 1752, when he travelled to just over half of Ireland's counties. He kept a record of this tour, but did not publish it. It ended up in the library of Trinity College, Dublin. Eventually, in 1891, an edited edition of Pococke's 1752 tour was published by George Thomas Stokes.
He was made bishop successively of Ossory, Elphin and of Meath in 1765. He spent many of his later years in travel throughout Britain and Ireland, publishing accounts of many of his journeys.
He died of apoplexy during a visitation at Charleville Castle, near Tullamore, County Offaly, Ireland, in 1765. On his death, many of his manuscripts were given to the British Library.
He was buried at Ardbraccan, County Meath, Ireland.