He now devoted himself to an exact study of biblical and patristic writers, especially Basil and Chrysostom. The result of this reading, and of the influence of John Wilkins, master of Trinity College, Cambridge, was seen in the general tone of his preaching, which was practical rather than theological, concerned with issues of personal morality instead of theoretical doctrine. This plain style of preaching is reflective of the late 17th century, when the integration of reason into Protestant theology came to be seen as one of its finest attributes against Roman Catholicism.
He was a man of the world as well as a divine, and in his sermons he exhibited a tact which enabled him at once to win the ear of his audience. In 1664 he became preacher at Lincoln's Inn. The same year he married Elizabeth French, a niece of Oliver Cromwell; and he also became Tuesday lecturer at St Lawrence, Jewry (where he was later buried). Tillotson employed his controversial weapons with some skill against atheism and Catholicism. In 1663 he published a characteristic sermon on "The Wisdom of being Religious," and in 1666 replied to John Sergeant's Sure Footing in Christianity by a pamphlet on the "Rule of Faith." The same year he received the degree of D.D.
It was chiefly through his advice that the king appointed an ecclesiastical commission for the reconciliation of the Dissenters. In August of this year he was appointed by the chapter of his cathedral to exercise the archiepiscopal jurisdiction of the province of Canterbury during the suspension of Sancroft. He was also about the same time named dean of St Paul's. Soon afterwards he was elected to succeed Sancroft; but accepted the promotion with extreme reluctance, and it was deferred from time to time, at his request, until April 1691. In 1693 he published four lectures on the Socinian controversy. His attempts to reform certain abuses of the Church, especially that of clerical non-residence, awakened much ill-will, and of this the Jacobites took advantage, pursuing him to the end of his life with insult and reproach. He died on 22 November 1694.
For his manuscript sermons Tillotson's widow received 2500 guineas. Ralph Barker edited some 250 of them together with the "Rule of Faith" (1695-1704). In 1752 an edition appeared in 3 vols., with Life by Thomas Birch, compiled from Tillotson's original papers and letters. Various selections from his sermons and works have been published separately. AMS Press, New York, published a modern edition of his works in the 1980s. In his home town of Sowerby, a statue of Tillotson still exists in St. Peter's church and an avenue is named after him in the lower end of the town.