This study develops a comprehensive and integrative framework for agile leadership in knowledge-based organizations (KBOs), designed to address the unique challenges of operating in volatile, uncertain, complex, and ambiguous (VUCA) environments. Drawing from the knowledge-based view (KBV) of the firm, dynamic capabilities theory, and contemporary agile leadership models, the framework emphasizes the interplay between leadership behaviors, organizational culture, and knowledge management processes. Specifically, it integrates the “align–empower” leadership paradigm, which balances strategic alignment with team empowerment, and incorporates transformational leadership as a catalyst for innovation, trust, and resilience. The framework operationalizes Nonaka and Takeuchi’s SECI model of knowledge creation (Socialization, Externalization, Combination, Internalization) within agile contexts, highlighting the role of leaders in creating an enabling environment (“Ba”) for knowledge sharing, learning, and application. By fostering psychological safety, autonomy, and shared purpose, agile leaders can accelerate both the creation and utilization of organizational knowledge, enhancing adaptability, responsiveness, and innovation. This synthesis offers theoretical contributions by bridging agile leadership and KBV perspectives, while providing practical guidelines for leadership development, digital transformation, and cultural change in KBOs. Implications extend to small and medium-sized enterprises (SMEs) and large-scale knowledge-intensive organizations, with recommendations for context-specific adaptation. The proposed model serves as a roadmap for scholars seeking to empirically test agile leadership mechanisms and for practitioners aiming to embed agility into the DNA of knowledge-driven enterprises. Ultimately, this framework underscores that in knowledge-based economies, agility in leadership is not optional—it is an imperative for sustained competitive advantage.