Cultivar mixtures have been proposed as a way to increase diversity and thereby improve plant production, but our understanding of the effects of mixing cultivars on crop diseases and resource-use efficiency remains fragmentary. We performed a meta-analysis to assess the effects of cultivar mixtures on crop yield, yield stability, resource-use efficiency, and disease severity compared with monocultures of twelve major crops. We found that, overall, mixing of cultivars increased crop yield by 3.82%. Yield gains from mixing cultivars were highest in rice (+16.1%), followed by maize (+8.5%), and were lowest in barley (+0.9%) and sorghum (no increase). Temporal yield stability increased with the number of cultivars in the mixtures. Overall, mixing cultivars increased crop biomass, leaf area index, photosynthetic rate, and Water-use efficiency by 5.1, 7.2, 8.5 and 4.3%, respectively, and decreased disease incidence by 24.1%. Cultivar mixtures were more effective in mitigating diseases and increasing yields in studies performed at lower latitudes, higher mean annual temperatures, and higher mean annual precipitation. Our study complements and adds to previous research, indicating that cultivar mixtures reduce crop losses to disease and enhance resource-use efficiency compared with monocultures globally. We conclude that the targeted use of cultivar mixtures with appropriate management practices can reduce resource and pesticide inputs while maintaining high yields, thereby promoting sustainable and productive agriculture. Graphical abstract: (Figure presented.)