Companies are increasingly adopting practices aimed at fostering intrapreneurial initiatives to ensure their survival, seize opportunities, and combat threats. This paper analyzes the effect of employee perceptions of high-performance work systems on intrapreneurial behavior, with potential mediation by knowledge management processes. It also analyzes possible moderation by human resource management (HRM) strength. Hypotheses were tested using partial least squares path modeling (PLS-PM) in Smart PLS 3.3. The analysis was conducted for a sample of 1,885 knowledge-intensive employees working in three banks in Ecuador. The results show that innovative behavior can be enhanced by implementing high-performance work systems. These systems promote sound knowledge management processes. These findings are relevant because they offer guidance to help practitioners promote intrapreneurship. They highlight the importance of high-performance work systems that enhance knowledge management processes, particularly knowledge sharing. The results also show that HRM strength moderates the relationships between high-performance work systems and intrapreneurial behavior and between knowledge management and intrapreneurial behavior. However, in the second of these relationships, the effect is the opposite of what is to be expected. This finding may indicate a need to consider this variable at the group, department, or even organizational level under a multilevel analysis approach.