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Background: Decision-making deficits in obesity and alcohol use disorder (AUD) may contribute to the choice of immediate rewards despite their long-term deleterious consequences., Methods: Gambling task functional MRI in Human connectome project (HCP) dataset was used to investigate neural activation differences associated with reward or punishment (a key component of decision-making behavior) in 418 individuals with obesity (high BMI) and without obesity (lean BMI) and either at high (HR) or low (LR) risk of AUD based on their alcohol drinking levels., Results: Interaction between BMI and alcohol drinking was seen in regions of the default mode network (DMN) and those implicated in self-related processing, memory, and salience attribution. ObesityHR relative to obesityLR also recruited DMN along with primary motor and regions implicated in inattention, negative perception, and uncertain choices, which might facilitate impulsive choices in obesityHR. Furthermore, obesityHR compared to leanHR/leanLR also demonstrated heightened activation in DMN and regions implicated in uncertain decisions., Conclusions: These results suggest that BMI is an independent variable from that of alcohol drinking levels in neural processing of gambling tasks. Moreover, leanLR relative to leanHR, showed increased activation in motor regions [precentral and superior frontal gyrus] suggestive of worse executive function from excessive alcohol use. Delayed discounting measures failed to distinguish between obesity and high alcohol drinking levels, which as for gambling task results suggests independent negative effects of obesity and chronic alcohol drinking on decision-making. These findings highlight distinct associations of obesity and high-risk alcohol drinking with two key constituents of decision-making behavior., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)