The purpose of the study was to examine the role of objective and subjective measures of neighborhood crime and disorder on substance use among a nationally representative sample of 4525 Jamaicans aged 12–65 years. Log-Poisson models with generalized estimating equations were used to estimate relative risks (RR) and 95% confidence intervals (CI). A test of interaction was used to determine presence of effect modification by sex. Approximately 39% of the study population reported past-month alcohol use; 10% past-month tobacco use; and 15% past-month marijuana use. In fully adjusted models, past-month alcohol and tobacco use were associated with perceived neighborhood disorder (p<0.05). The likelihood of alcohol use was 1.12 (95%CI:1.04, 1.20) times greater among participants who perceived higher neighborhood disorder. The likelihood of tobacco use was 1.22 (95%CI: 1.01, 1.46) times greater among participants who perceived higher neighborhood disorder. A significant test for interaction in adjusted models (P<0.2) suggested that the associations between substance use and perceived neighborhood disorder varied by sex. Examination of stratified models indicated that the role of perceived neighborhood disorder on alcohol and tobacco consumption varied among females, but not males. Females who perceived higher levels of neighborhood disorder had an increased likelihood of past-month alcohol and tobacco use (RRa:1.25 95%CI:1,07, 1.45; RRa:1.73 95%CI: 1.10, 2.67). Objective neighborhood crime measures were not associated with alcohol, tobacco, or marijuana use. The study findings provide evidence for the importance of considering subjective and objective neighborhood measures when examining relations with health outcome and demonstrate that perceptions of context and contextual exposures are not uniform across populations within neighborhoods. Interventions focused on building community trust and social cohesion (e.g. neighborhood community watch groups) and greening of blighted or abandoned spaces may help increase the sense of safety and order, reducing stress and maladaptive coping such as substance use.