The Nicene-Constantinopolitan Creed’s affirmation that Jesus Christ “by the Holy Spirit was incarnate of the Virgin Mary” reflects a deeply biblical and theologically rich claim about the person and work of the Holy Spirit. By retrieving and clarifying the Creed’s brief but profound affirmation, this paper helps illuminate the Spirit’s identity as the Lord and giver of life who uniquely sets apart the incarnate Son as holy. This study contributes to trinitarian theology and pneumatology by demonstrating that the Spirit’s role in the incarnation is both foundational to understanding the person of Christ and emblematic of the Spirit’s wider work in creation, providence, and redemption. Drawing from Matthew 1:18–25 and Luke 1:35 in particular and engaging theological voices including John Owen, Abraham Kuyper, Stephen Wellum, and others, this paper explores the Spirit’s creative and sanctifying role in both ordinary and extraordinary generation to articulate how the Spirit’s overshadowing of Mary points to a work that is not merely biological but covenantal and Christological. Specifically, the Spirit’s overshadowing of Mary, while consistent with the doctrine of inseparable operations, is a uniquely personal work in which the Spirit acts as the giver of life and the sanctifier of the human nature assumed by the Son. Theologians disagree about how exactly the Spirit is or is not the Creator of the human nature or body of Jesus, and how his role in the incarnation relates to the Father and the Son, leading to several apparently inconsistent understandings of what the Creed and Scripture assert. Although theologians emphasize different aspects of the Holy Spirit’s role in the incarnation that are sometimes thought to be mutually exclusive, I argue that the Spirit’s role in the incarnation is best understood as a convergence of three biblical and theological themes: the Spirit’s life-giving power as God, his sanctifying presence, and his participation in the new covenant creation.