Perceived control is strongly related to mental health and well-being. Specifically, lack of perceived control has been associated with learned helplessness and stress-related disorders, such as depression and anxiety. However, it is unknown whether brain activation to control and its protective effect against stress can predict changes in quality of life. To address this gap, we examined the neural underpinning of controllability in healthy females (N=40) performing the Value of Control task in an fMRI scanner. Quality of life and perceived stress were assessed at baseline and 6-month follow-up. Increased brain activation for control was found within the putamen, insula, thalamus, mid-cingulate, dorsolateral prefrontal cortex, motor cortex, and cerebellum. In contrast, increased brain activation for lack of control was found within the posterior cingulate and prefrontal cortices. In an exploratory analysis, an elastic-net algorithm was used to identify brain predictors of quality of life 6 months later. The right putamen's activation to control was selected as the best prospective predictor of improvement in life enjoyment and satisfaction and this association was mediated by changes in perceived stress. Our findings suggest that neural responsiveness to control may have utility as a potential marker of quality of life and resilience to adversity.