Clarke afterwards devoted himself to the study of Scripture in the original, and of the primitive Christian writers. Having taken holy orders, he became chaplain to John Moore (1646-1714), bishop of Norwich, who was ever afterwards his friend and patron. In 1699 he published two treatises,--one entitled _Three Practical Essays on Baptism, Confirmation and Repentance_, and the other, _Some Reflections on that part of a book called Amyntor, or a Defence of Milton's Life, which relates to the Writings of the Primitive Fathers, and, the Canon of the New Testament_. In 1701 he published _A Paraphrase upon the Gospel of St Matthew_, which was followed, in 1702, by the _Paraphrases upon the Gospels of St Mark and St Luke_, and soon afterwards by a third volume upon St John. They were subsequently printed together in two volumes and have since passed through several editions. He intended to treat in the same manner the remaining books of the New Testament, but his design was unfulfilled.
Meanwhile he had been presented by Bishop Moore to the rectory of Drayton, near Norwich. As Boyle lecturer, he dealt in 1704 with the _Being and Attributes of God_, and in 1705 with the _Evidences of Natural and Revealed Religion_. These lectures, first printed separately, were afterwards published together under the title of _A Discourse concerning the Being and Attributes of God, the Obligations of Natural Religion, and the Truth and Certainty of the Christian Revelation, in opposition to Hobbes, Spinoza, the author of the Oracles of Reason, and other Deniers of Natural and Revealed Religion_.
In 1706 he wrote a refutation of Dr Henry Dodwell's views on the immortality of the soul, and this drew him into controversy with Anthony Collins. He also wrote at this time a translation of Newton's _Optics_, for which the author presented him with £500. In the same year through the influence of Bishop Moore, he obtained the rectory of St Benet's, Paul's Wharf, London. Soon afterwards Queen Anne appointed him one of her chaplains in ordinary, and in 1709 presented him to the rectory of St James's, Westminster. He then took the degree of doctor in divinity, defending as his thesis the two propositions: _Nullum fidei Christianae dogma, in Sacris Scripturis traditum, est rectae rationi dissentaneum_, and _Sine actionum humanarum libertate nulla potest esse religio_. During the same year, at the request of the author, he revised Whiston's English translation of the _Apostolical Constitutions_.