There is growing interest in the role of psychosocial stress in health disparities. Identifying which social stressors are most important to community residents is critical for accurately incorporating stressor exposures into health research. Using a community-academic partnered approach, we designed a multi-community study across the five boroughs of New York City to characterize resident perceptions of key neighborhood stressors. We conducted 14 community focus groups; two to three in each borough, with one adolescent group and one Spanish-speaking group per borough. We then used systematic content analysis and participant ranking data to describe prominent neighborhood stressors and identify dominant themes. Three inter-related themes regarding the social and structural sources of stressful experiences were most commonly identified across neighborhoods: (1) physical disorder and perceived neglect, (2) harassment by police and perceived safety and (3) gentrification and racial discrimination. Our findings suggest that multiple sources of distress, including social, political, physical and economic factors, should be considered when investigating health effects of community stressor exposures and psychological distress. Community expertise is essential for comprehensively characterizing the range of neighborhood stressors that may be implicated in psychosocial exposure pathways.