Objectives A cline of frequencies of the derived allele of the ALDH2 gene, which causes a deficiency of an enzyme and “facial flushing” in humans who drink alcohol, has been known among the people of the Japanese archipelago. This cline is conventionally explained by admixture with immigrants from the Asian continent occurring during the Yayoi period. Previous studies lack sufficient data from the peripheral regions of the indigenous Jomon people, and those data the ADH1B gene that is involved in the Class I ADH gene cluster and contains another variant leading to a functional change. Methods We focused on the southwestern‐most people from the Ryukyu Islands (n = 218) and those from northern Kyushu (n = 21) where the Yayoi immigrants likely arrived. We investigated both the Class I ADH and ALDH2 loci, as well as neutral genetic markers. Results In the Ryukyu Islands, the frequencies of the ancestral alleles in both loci were always higher than those in mainland Japan, while the frequencies of ADH1B were less than those of the derived allele. A haplotype block was not observed in ALDH2 but was in Class I ADH. Discussion Our data suggest that the derived allele of ALDH2 came with the Yayoi immigrants from the Asian continent to the Japanese archipelago. However, the derived allele of ADH1B is unlikely to be related to the Yayoi migration. Therefore, we postulate that the expansion of the derived allele of ADHIB in East Asia could be traced back to the last glacial period.