As AI models scale to billions of parameters and operate with increasing autonomy, ensuring their safe, reliable operation demands engineering-grade security and assurance frameworks. This paper presents an enterprise-level, risk-aware, security-by-design approach for large-scale autonomous AI systems, integrating standardized threat metrics, adversarial hardening techniques, and real-time anomaly detection into every phase of the development lifecycle. We detail a unified pipeline - from design-time risk assessments and secure training protocols to continuous monitoring and automated audit logging - that delivers provable guarantees of model behavior under adversarial and operational stress. Case studies in national security, open-source model governance, and industrial automation demonstrate measurable reductions in vulnerability and compliance overhead. Finally, we advocate cross-sector collaboration - uniting engineering teams, standards bodies, and regulatory agencies - to institutionalize these technical safeguards within a resilient, end-to-end assurance ecosystem for the next generation of AI.