Multi-genotype varieties can effectively alleviate or reverse the decline of genetic diversity in agriculture caused by the predominant extension of mono-genotype (pure line) varieties of crop plants. We devised a novel breeding strategy for developing multi-genotype varieties of rice from MAGIC lines, which were derived from two convergent crosses among 8 or 12 parental lines, respectively. We found that both multi-genotype varieties and varietal mixtures were superior to their component lines/varieties in both yielding and blast-resistance performances. When the multi-genotype varieties were developed through intensive selection, they displayed comparable or better performance in yielding level and disease resistance in comparison to current leading mono-genotype varieties of rice. A promising multi-genotype variety has been selected over a 2-year regional trial in Hainan province and it will be hopefully granted a varietal-release permit. Multi-genotype breeding may be an alternative and feasible solution to the sustainable development of agriculture.