Alcohol use disorder (AUD) is a chronic, relapsing condition with poor treatment outcomes. Both alcohol craving and negative affect increase alcohol drinking, and-in healthy adults-can be attenuated using cognitive strategies, which rely on the prefrontal cortex (PFC). However, AUD is associated with cognitive impairments and PFC disruptions. Thus, we tested whether individuals with AUD can successfully recruit the PFC to effectively regulate craving and negative emotions, whether neural mechanisms are shared between the two types of regulation, and whether individual differences influence regulation success. During functional magnetic resonance imaging, participants with AUD completed the regulation of craving task (n = 17) that compares a cue-induced craving condition with an instructed regulation condition. They also completed the emotion regulation task (n = 15) that compares a negative affect condition with an instructed regulation condition. Regulation strategies were drawn from cognitive behavioral therapy treatments for AUD. Self-reported craving and negative affect were collected on each trial. Individuals with AUD effectively regulated their craving and negative affect when instructed to do so using cognitive behavioral therapy-based strategies. Regulation was associated with recruitment of both common and distinct PFC regions across tasks, as well as with reduced activity in regions associated with craving and negative affect (e.g., ventral striatum, amygdala). Effective regulation of craving was associated with negative alcohol expectancies. Both common and distinct regulatory systems underlie regulation of craving and negative emotions in AUD, with notable individual differences. This has important implications for AUD treatment.