John Owen was one of the most significant theologians in British history. He exemplifies British Reformed orthodox theology at its height. The relationship between exegesis and theology in Reformed orthodoxy is often a neglected topic in secondary literature. This article examines Owen's exegesis of Genesis 3:15 in its international historical context to demonstrate the close relationship between theology and exegesis in the Reformed tradition. This analysis will better enable historians to reassess common misconceptions of Reformed orthodoxy and to equip theologians to draw potentially from Owen and others as a historical model for doing theology. John Owen was one of the most significant theologians in British history. He exemplifies British Reformed orthodox theology at its height. The relationship between exegesis and theology in Reformed orthodoxy is often a neglected topic in secondary literature. This article examines Owen's exegesis of Genesis 3:15 in its international historical context to demonstrate the close relationship between theology and exegesis in the Reformed tradition. This analysis will better enable historians to reassess common misconceptions of Reformed orthodoxy and to equip theologians to draw potentially from Owen and others as a historical model for doing theology.