A meta-analysis reveals that cultivar mixtures globally increase crop yields by 3.82%, with the highest gains in rice (+16.1%) and the lowest in barley (+0.9%). Temporal yield stability increases with more cultivars in mixtures. Cultivar mixtures also boost biomass, leaf area index, photosynthetic rate, and water-use efficiency by 5.1, 7.2, 8.5, and 4.3%, respectively, and reduce disease incidence by 24.1%. These benefits are more pronounced in lower latitudes, higher mean annual temperatures, and higher mean annual precipitation. The study highlights that cultivar mixtures reduce crop losses to disease and improve resource-use efficiency compared to monocultures. They can reduce resource and pesticide inputs while maintaining high yields, promoting sustainable agriculture. Cultivar mixtures are more accessible than intercropping for large, mechanized farms, offering increased diversity without changing agronomic practices. Previous meta-analyses showed yield increases of 2.2–3.5%, but this study is the first to comprehensively analyze the effects of cultivar mixtures on resource efficiency and disease severity across 12 major crops. The study used 103 studies, including data from 103 publications, and analyzed parameters like yield, leaf area index, photosynthetic rate, water-use efficiency, disease index, and area under the disease progress curve. Environmental factors and mixture components were analyzed for their relationships with yield and other traits. The study acknowledges limitations in data availability but uses widely accepted metrics like annual average temperature and precipitation. Plant traits used in mixtures were categorized as disease or physical or both, based on breeding history, growth habits, and disease resistance. The findings suggest that targeted use of cultivar mixtures with appropriate management can enhance agricultural sustainability.A meta-analysis reveals that cultivar mixtures globally increase crop yields by 3.82%, with the highest gains in rice (+16.1%) and the lowest in barley (+0.9%). Temporal yield stability increases with more cultivars in mixtures. Cultivar mixtures also boost biomass, leaf area index, photosynthetic rate, and water-use efficiency by 5.1, 7.2, 8.5, and 4.3%, respectively, and reduce disease incidence by 24.1%. These benefits are more pronounced in lower latitudes, higher mean annual temperatures, and higher mean annual precipitation. The study highlights that cultivar mixtures reduce crop losses to disease and improve resource-use efficiency compared to monocultures. They can reduce resource and pesticide inputs while maintaining high yields, promoting sustainable agriculture. Cultivar mixtures are more accessible than intercropping for large, mechanized farms, offering increased diversity without changing agronomic practices. Previous meta-analyses showed yield increases of 2.2–3.5%, but this study is the first to comprehensively analyze the effects of cultivar mixtures on resource efficiency and disease severity across 12 major crops. The study used 103 studies, including data from 103 publications, and analyzed parameters like yield, leaf area index, photosynthetic rate, water-use efficiency, disease index, and area under the disease progress curve. Environmental factors and mixture components were analyzed for their relationships with yield and other traits. The study acknowledges limitations in data availability but uses widely accepted metrics like annual average temperature and precipitation. Plant traits used in mixtures were categorized as disease or physical or both, based on breeding history, growth habits, and disease resistance. The findings suggest that targeted use of cultivar mixtures with appropriate management can enhance agricultural sustainability.