The Chemistry and Metallurgy Research Replacement (CMRR) Project under development at Los Alamos National Laboratory is being executed under a variety of Quality Assurance Requirements, DOE Orders, and CFR Regulations for the design, construction, and testing of all physical aspects of the CMRR Project. This unique US Nuclear Defense Project is the most significant new nuclear weapons infrastructure development since inception of the Manhattan Engineering District Program in the 1940’s. Those unclassified aspects of QA requirements and procedures implemented for this major project are presented and assessed for meeting the demanding requirements imposed to ensure safety, reliability, and success of this vital facility to secure US Nuclear Defense in the 21st century.