Many features are shared between esophageal cancer (EC) and gastric cancer (GC). This study aimed to explore whether known EC susceptibility loci are also important in the development of GC. A total of 21 genetic variants associated with EC in genome-wide association studies were evaluated with association of GC risk in 2631 cases and 4373 controls of Chinese ancestry. Single variant and weighted genetic scores (WGS) for esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), and overall EC were analyzed with GC risk, respectively. Genetic variants of rs2274223 in PLCE1 at 10q23.33 (per G allele: odds ratio (OR) = 1.26, 95% confidence interval (CI): 1.16-1.38, P = 6.51 × 10-8), rs10052657 in PDE4D at 5q11.2 (per C allele: OR = 1.12, 95% CI: 1.01-1.25, P = 3.28 × 10-2) and rs671 in ALDH2 at 12q24.12 (per A-allele: OR = 0.83, 95% CI: 0.75-0.91, P = 1.14 × 10-4) were significantly associated with GC risk. The combined effect of those three variants had stronger influence on GC risk (OR = 1.31, 95% CI: 1.19-1.44, P = 2.34 × 10-8). High WGS of ESCC was also associated with increased risk of GC (P = 5.52 × 10-4 as a continuous variable) (trend test P = 2.71 × 10-4), whereas no statistically significant associations were observed between the WGS of EAC and GC risk (P = 0.66 as a continuous variable) (trend test P = 0.70). ESCC rather than EAC may share genetic susceptibility with GC. Genetic variants at 10q23.33, 5q11.2, and 12q24.12 may be useful as biomarkers to identify individuals with high risk for both ESCC and GC.