The LCMS affirms the Protestant biblical canon consisting of 66 books: 39 Old Testament books (following the Hebrew canon) and 27 New Testament books. The Old Testament includes the five books of Moses (Pentateuch), the historical books, the wisdom literature, and the prophetic books, arranged in the traditional Protestant order.

The LCMS explicitly rejects the deuterocanonical books (Apocrypha)—books such as Tobit, Judith, 1 and 2 Maccabees, Wisdom of Solomon, Ecclesiasticus (Sirach), and others found in Roman Catholic and Eastern Orthodox canons. While Martin Luther permitted reading these books for edification (as 'useful for information' but 'not in the realm of those books which are held to be divine'), they are not recognized as authoritative Scripture or binding for doctrine.

The canon is considered closed; no additional books are being added to Scripture. The books within the canon are recognized as genuinely inspired by God and are the authoritative standard for faith and practice. The criteria for canonicity include apostolicity (connection to an apostle or apostolic tradition), content (conformity with apostolic doctrine), and reception (acceptance by the early church). All 66 books meet these criteria and are received as the complete and sufficient Word of God.