Quitting smoking is notoriously difficult. Models of nicotine dependence posit that deficits in cognitive control contribute to failures to maintain smoking abstinence during smoking cessation attempts. We examine the role for large-scale functional brain systems associated with cognitive control in smoking lapse. We use data from 70, five-minute functional magnetic resonance imaging (fMRI) scans in 17 daily smokers (5 female) undergoing a smoking lapse paradigm after 12 hours of smoking abstinence. Cox regression results indicate that decreased segregation of the default mode system from the frontoparietal system undermine the ability to resist smoking. Results lend support to the hypothesis that large-scale functional brain systems associated with cognitive control are implicated in smoking lapse behavior and point to the importance of cognitive control as a mechanism underlying smoking relapse.