Cloning quantitative trait locus (QTL) is time consuming and laborious, which hinders the understanding of natural variation and genetic diversity. Here, we introduce RapMap, a method for rapid multi-QTL mapping by employing F2 gradient populations (F2GPs) constructed by minor-phenotypic-difference accessions. We have updated the concept of Mendel's single gene segregation into 12 single-locus genetic models in RapMap according to three different genetic effects, and found that they share the common and general nature, the co-segregation standard. The co-segregation standard of the single-locus genetic models ensures simultaneous integration of a three-in-one framework in RapMap i.e. detecting a real QTL, confirming its effect, and obtaining its near-isogenic line-like line. A genetic population that does not meet the co-segregation standard could be replaced by a phenotype-well-segregating F3 or F4 family. We demonstrate the feasibility of RapMap by cloning 20 grain-size and 18 grain-chalkiness genes in rice using 65 F2GPs in three years. These genes explain a total of 75% of phenotype variation, revealing the major genetic basis of rice appearance quality traits. The co-segregation standard, which serves as the necessary and sufficient condition of single-locus genetic models, is the cornerstone of RapMap, while the construction of multiple F2GPs to most probably meet the quality-control standard is its technical strategy. Thus, the co-segregation standard coupled with multiple F2GPs ensures that RapMap can be applied to any plants and animals that are easy to crossbreed and reproduce to rapidly and comprehensively uncover the general molecular basis underlying genetic diversity of important traits.