The CRCNA affirms the Holy Spirit as the third person of the Trinity, fully divine and coequal with the Father and Son. The Spirit's work includes applying the benefits of Christ's redemption to believers through regeneration and faith, indwelling believers to effect sanctification, and empowering the church for witness and service. The Heidelberg Catechism (Q&A 53) teaches that the Spirit is given to believers for assurance and comfort, dwelling in their hearts and sealed until the day of redemption.

The CRCNA holds a generally cessationist view of the miraculous gifts of the Spirit. While affirming that the Spirit sovereignly distributes gifts according to his will, the CRCNA has historically been cautious about claims to continuing prophecy, healing, or speaking in tongues as normative evidence of the Spirit's work. The Spirit's primary work is sanctification through the Word and sacraments, not extraordinary signs and wonders.

A distinctive emphasis in CRCNA theology is the Spirit's role in worldview formation and cultural transformation. The CRCNA teaches that believers, indwelt by the Spirit, are called to carry Christian conviction into all of life — education, work, art, science, and civic engagement. The Spirit empowers this 'worldview' transformation, equipping believers to live as a covenant people and to work toward the transformation of culture in light of Christ's lordship.