Background: Rapid urbanization has contributed to increasingly sedentary lifestyles, which may independently influence metabolic health. While physical inactivity is a known risk factor for insulin resistance (IR), the specific contribution of prolonged sedentary behavior to IR in urban adults remains incompletely synthesized. This systematic review and meta-analysis aimed to evaluate the association between sedentary lifestyle and insulin resistance among urban adult populations. Methods: A systematic search of PubMed/MEDLINE, Embase, Scopus, and Web of Science was conducted from inception to December 2025 following PRISMA guidelines. Observational and interventional studies involving adults (≥18 years) residing in urban settings were included if they assessed sedentary behavior quantitatively and reported validated measures of insulin resistance (HOMA-IR, fasting insulin, TyG index, Matsuda index, or clamp-derived indices). Adjusted effect estimates were extracted. Random-effects meta-analysis was performed for studies reporting comparable odds ratios (ORs) for high versus low sedentary exposure. Heterogeneity was assessed using the I² statistic. Results: Fourteen studies comprising 18,732 participants met inclusion criteria. Sedentary behavior was assessed using validated self-report tools (n=8) or accelerometry (n=6), and insulin resistance was primarily measured using HOMA-IR. Meta-analysis of five studies demonstrated that high sedentary time (≥8–10 hours/day) was associated with significantly higher odds of insulin resistance (pooled OR 1.33; 95% CI: 1.12–1.57; I² = 58%). Continuous outcome analysis showed a small-to-moderate increase in HOMA-IR among individuals with higher sedentary exposure (pooled standardized mean difference 0.29; 95% CI: 0.11–0.47). Associations remained significant after adjustment for adiposity and moderate-to-vigorous physical activity. Conclusions: Prolonged sedentary behavior is significantly associated with increased insulin resistance in urban adults, independent of conventional risk factors. Public health strategies should address not only insufficient physical activity but also excessive sitting time. Longitudinal and interventional studies using standardized measurement approaches are needed to further clarify causality and inform targeted urban health policies.