Pike was educated for the independent ministry, receiving his general training from John Eames of the Fund academy, and his theology from John Hubbard at Stepney academy. His first settlement was at Henley-on-Thames, Oxfordshire, about 1740. Thence he removed in 1747 to succeed John Hill (1711–1746) as pastor at the Three Cranes meeting-house in 'Fruiterers' Alley, Thames Street, London. Early in his London ministry he established, at his house in Hoxton Square, an academy for training students for the ministry. He adopted the principles of John Hutchinson (1674–1737), and defended them (1753) in a laborious work. In 1754 he succeeded Zephaniah Marryat, D.D. (1684?–1754),. as one of the Tuesday lecturers at Pinners' Hall. About the same time he joined Samuel Hayward (1718–1757), independent minister at Silver Street, Wood Street, Cheapside, in a Sunday-evening lecture, dealing with ‘cases of conscience,’ at Little St. Helen's, Bishopsgate Street. His ‘Body of Divinity’ (1755) was criticised by Caleb Fleming.
In 1757 Pike became acquainted with the views of Robert Sandeman, the son-in-law and disciple of John Glas. Sandeman had published (1757) a series of Letters dealing with the Dialogues between Theron and Aspasio (1755), by James Hervey (1714–1758). The Letters were admired by members of Pike's church; and Pike, on reading them, began (17 Jan. 1758) a correspondence with Sandeman, then in Edinburgh. The correspondence, as it proceeded, was communicated to Pike's church, with the result that he, and a section of his people, came gradually into Sandeman's views; while others showed such dissatisfaction that Pike ceased the correspondence, suppressing his fourth letter. He began, however, to adopt Glassite or Sandemanian usages, including a weekly communion. This led (August 1758) to rumours of his unsoundness; his discourses at Pinners' Hall gave offence, and he was excluded from the lectureship in 1759 by forty-four votes to one, Dr. John Conder being chosen to succeed him on 3 Oct. In his own church he was hotly opposed by William Fuller and Thomas Uffington. A church meeting (9 October 1759) came to no conclusion; church meetings on 13 January and 21 April 1760 were equally divided (seventeen votes on either side), but Pike's casting vote carried the exclusion of the malcontents, who formed a new church under Joseph Barber. Disputes then arose about possession of church property, and a lawsuit was begun (1761) by Pike for recovery of an endowment of £12 a year. At length he resigned his charge (14 December 1765), left the independents, and became a member of the Sandemanian church in Bull-and-Mouth Street, St. Martin's-le-Grand. He was chosen "elder" in 1766, and ministered with great acceptance.
From London Pike moved in 1771 to minister to a Sandemanian congregation at Trowbridge, Wiltshire. Unfounded reports were spread of his insobriety. Pike was a follower of the doctrines of Hutchinson, who found in scripture a system of physical science, and then became a follower of Glas, who held that biblical authority did not extend to such topics. He died at Trowbridge in January 1773, and was buried on 10 Jan. in the parish churchyard. His portrait, engraved by Hopwood, is given in Wilson. He was married, and left issue.
He published, besides single sermons (1748–53):
- Philosophia Sacra ... Natural Philosophy. Extracted from Divine Revelation, &c., 1753, 8vo; Edinburgh, 1815, 8vo.
- Thoughts on such Phrases of Scripture as ascribe ... Passions to the Deity, &c., 1753, 12mo.
- Some important Cases of Conscience, &c., 1755–6, 8vo, 2 vols. (the substance of lectures by Pike and Hayward); Glasgow, 1762, 8vo; with title ‘Religious Cases of Conscience, 1775, 8vo; 1807, 8vo; Romsey, 1819, 8vo; Philadelphia , 12mo; with title ‘The Doubtful Christian encouraged, &c., Woodbridge , 8vo; in Welsh, 1769, 12mo.
- A form of Sound Words; or ... Body of Divinity, &c., 1755, 12mo; 1756, 12mo (based on the shorter catechism of the Westminster assembly).
- Public Fasting, &c., 1757, 12mo; 1758, 8vo.
- An Epistolary Correspondence between ... Pike and ... Sandeman, &c., 1758, 8vo; in Welsh, 1765, 12mo.
- Saving Grace, Sovereign Grace, &c., 1758, 8vo (lectures at Pinners' Hall); 1825, 8vo.
- Free Grace indeed! &c., 1759, 8vo; 1760, 12mo.
- A ... Narrative of the ... Schism in the Church under ... Pike, &c., 1760, 8vo.
- Simple Truth Vindicated, &c., 1760, 12mo (anon).
- The Nature and Evidence of Saving Faith, &c., 1764, 8vo.
- A Plain ... Account of ... Practices observed by the Church in St. Martin's-le-Grand, &c., 1766, 8vo; 1767, 12mo.
- A Compendious Hebrew Lexicon, &c., 1766, 8vo (annexed is a short grammar); Glasgow, 1802, 8vo.
- "Marryatt, Zephaniah (c.1684-c.1754)". Dr Williams’s Centre for Dissenting Studies. 2011. Retrieved 21 December 2013.
- Gordon, Alexander (1900). "Pike, Samuel". In Lee, Sidney. Dictionary of National Biography 63. London: Smith, Elder & Co. "sources: [Wilson's Dissenting Churches of London, 1808, ii. 85 sq., 253; information from the parish register, Trowbridge, per the Rev. H. Trotter.]"