Major fecundity (Fec) genes play a central role in regulating the ovulation rate and litter size in sheep and have become important targets for genetic improvement programs. This study aimed to systematically evaluate the global evidence regarding the association of the major fecundity genes BMPR1B, BMP15, and GDF9 with litter size through a systematic review and meta-analysis. A total of 104 studies met the eligibility criteria for the systematic review, 31 of which provided sufficient quantitative data for meta-analysis. Random-effects models were used to compare litter size among genotypes, and subgroup analyses together with meta-regression were performed to investigate the contribution of gene identity, mutation type, climatic region, and production system to the observed between-study heterogeneity. Overall, heterozygous carriers of fecundity-associated polymorphisms produced significantly larger litters than wild-type animals. Gene-specific analyses showed that BMPR1B exhibited the strongest positive association with litter size, followed by BMP15, whereas GDF9 showed no significant overall pooled effect. Meta-regression identified gene identity (Pseudo-R² = 38.57%) and mutation type (Pseudo-R² = 31.12%) as the principal sources of between-study heterogeneity, while climatic region and production system had no significant moderating effects. These findings provide robust quantitative evidence supporting the use of validated fecundity-associated markers, particularly BMPR1B, in marker-assisted and genomic selection programs aimed at improving reproductive performance in sheep.