Neural imaging combined with physiological monitoring reveals that perceived control over stressful situations dampens cortisol release and inflammatory markers while activating prefrontal regulatory circuits. Participants who felt greater agency during laboratory stress tasks showed 30% lower stress hormone spikes and reduced activation in threat-processing brain regions compared to those experiencing identical stressors without perceived control. This biological validation of a psychological construct has profound implications for stress resilience training. Unlike genetic factors or major life circumstances, perceived control represents a modifiable cognitive skill that adults can develop through mindfulness practices, cognitive behavioral therapy, or structured exposure exercises. The findings align with decades of research linking internal locus of control to better health outcomes, but this study provides the neurobiological mechanism. For health-conscious adults facing chronic workplace stress or caregiving demands, cultivating a sense of agency—even over small daily decisions—may offer measurable protection against stress-related inflammation and hormonal dysfunction. The research suggests that stress management interventions should focus less on eliminating stressors and more on building psychological resources for navigating unavoidable challenges with greater perceived control.