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Abstract This chapter situates Isaac Newton’s reflections on science and religion within the Early Modern landscape by outlining ten historical models of science-religion relations and presenting a four-ring methodological framework for interpreting his texts. It surveys Newton’s vast manuscript corpus—from early prophetic writings and “De gravitatione” to the Principia, Opticks, Classical Scholia, Bentley letters, and the General Scholium—to show how he develops principles that distinguish philosophical and natural theology from revealed doctrine. The chapter demonstrates that Newton articulates a policy of independence by separating natural philosophy from matters grounded in divine will, while also showing that he permits integration through natural theology, design arguments, fine-tuning claims, and appeals to the phenomena. It explains how Newton employs the Two Books analogy, hermeneutics of accommodation, prophetic rules, empiricism, and simplicity to connect the interpretation of Scripture with the study of nature while preserving disciplinary boundaries. Finally, the chapter argues that Newton resolves science-religion relations through a dual framework in which natural philosophy supports higher-order theism, whereas lower-order doctrinal theology remains anchored in revelation and thus stands outside philosophical inquiry.