Background: Coronary artery disease (CAD) remains a major cause of morbidity and mortality worldwide. Variants in the lipid metabolism gene SCARB1 may influence CAD susceptibility, but existing evidence is inconsistent. Methods: We systematically searched PubMed, Embase, Web of Science, the Cochrane Library, and Scopus up to 13 February 2026 for case–control studies on SCARB1 polymorphisms and CAD risk. Three polymorphisms, rs5888, rs4238001, and rs10846744, were included. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated under multiple genetic models. Subgroup analyses were conducted for rs5888 by sex, ethnicity, and clinical outcome. Heterogeneity was assessed using I². Results: 12 eligible case–control studies involving 3947 CAD cases and 5076 controls were included. Overall, rs5888 was not significantly associated with CAD in any genetic model, either in the pooled analysis or in subgroup analyses by ethnicity and clinical outcome. In sex-stratified analyses, males carrying the TT genotype had a significantly lower CAD risk under the recessive model (OR = 0.73, 95% CI: 0.57–0.93), whereas no significant association was observed in females. No significant association was found between rs4238001 and CAD under any model. In contrast, the rs10846744 G allele was significantly associated with reduced CAD risk under the allelic (OR = 0.78, 95% CI: 0.64–0.94), dominant (OR = 0.68, 95% CI: 0.50–0.93), homozygote (OR = 0.65, 95% CI: 0.44–0.94), and additive models (OR = 0.80, 95% CI: 0.67–0.96). Conclusions: SCARB1 rs5888 showed a male-specific association with CAD, while rs10846744 showed a suggestive inverse association that requires further validation.