Background: Neighborhood and psychosocial variables are related to physical activity (PA), yet interactions between these factors in predicting PA are infrequently studied. Methods: This analysis examines the independent associations and interactions between self-reported neighborhood and psychosocial variables in relation to moderate to vigorous PA (MVPA) among adults from a US panel sample. Results: In adjusted models, neighborhood social capital was positively associated with meeting MVPA guidelines. Fewer barriers, greater self-efficacy, and greater autonomous motivation also corresponded with greater odds of meeting MVPA guidelines. An interaction between social capital and autonomous motivation showed that social capital was only associated with MVPA when autonomous motivation was high. Participants who reported both high autonomous motivation and high social capital were most likely to meet MVPA guidelines. Conclusions: Neighborhood social capital, barriers, self-efficacy, and autonomous motivation may be important correlates in promoting adults’ PA. Future directions include using objective neighborhood and PA data in similar analyses and investigating associations of neighborhood and psychosocial variables with multiple PA activities. Intervention research to promote PA should also examine whether effects of interventions targeting psychosocial constructs are moderated by features of an individual’s neighborhood or whether perceived social capital can be addressed in interventions in conjunction with psychosocial variables.