Stress and negative affect are known contributors to drug use and relapse, and several known treatments for addictions include strategies for managing them. In the current study, we administered a well-established stress provocation during functional magnetic resonance imaging (fMRI) to 23 participants who completed either mindfulness training (MT; N=11) or the American Lung Association's Freedom From Smoking (FFS; N=12), which is a cognitive-behavioral treatment (CBT) for smoking cessation. Across the entire sample, we found that stress reactivity in several brain regions including the amygdala and anterior/mid insula was related to reductions in smoking after treatment, as well as at 3-month post-treatment follow-up. Moreover, conjunction analysis revealed that these same regions also differentiated between treatment groups such that the MT group showed lower stress-reactivity compared to the FFS/CBT group. This suggests that reduction in stress reactivity may be one of the mechanisms that underlie the efficacy of MT in reducing smoking over time. The findings have important implications for our understanding of stress, the neural and psychological mechanisms that underlie mindfulness-based treatments, and for smoking cessation treatments more broadly.