With almost 38% of the adult population in the United States meeting the criterion for obesity, weight loss has become a public health concern. However, we are not yet able to predict who will succeed in losing weight through dietary interventions. Intrinsic characteristics, such as neural sensitivity to rewards, may be important features related to why some people lose weight but others do not. The aim of the current study was to examine whether neural reward network responsivity to visual food cues before beginning a 12-month energy restriction regimen predicted weight loss. 108 middle aged (mean age = 44.75+8.55 years), overweight and obese adults (mean baseline BMI = 30.93+3.59 kg/m2) participated in a 12-month, dietary weight-loss intervention. Participants underwent structural and functional neuroimaging at baseline, which included a visual food cuing (VFC) task to elicit neural responses to rewarding stimuli. The VFC task included conditions when participants saw images of highly-caloric foods, low-caloric foods, and neutral images. Statistical maps of the changes in BOLD signal during high-caloric foods vs. fixation, high- vs. low-caloric foods, and food vs. neutral image contrasts were used to examine neural sensitivity to reward. On average, participants lost 9% of their initial body weight at the end of the intervention (mean % of weight loss = 9.06+6.86%; mean change in BMI = -2.74+2.23 kg/m2). In the high-caloric > fixation and high-caloric > low-caloric contrasts, positive associations were seen between changes in BOLD signal and percentage of weight lost in the bilateral anterior cingulate cortex (ACC). In the food > neutral image contrast, negative associations were seen between changes in BOLD signal and percentage of weight lost in the right caudate nucleus, right dorsolateral prefrontal cortex, and right orbitofrontal cortex. For overweight and obese individuals, heightened sensitivity to food-related cues in reward regions of the brain is associated with less weight lost over 12 months. These same cues elicit increased response in brain areas associated with conflicting stimuli, which may suggest that overweight and obese adults who are more successful at losing weight are better able to ignore the temptation of rewarding foods in the context of a dietary intervention.