Abstract: To quantitatively analyze the impact of foliar Se application on grain yield, quality, and Se accumulation in winter wheat in China, 41 published studies (36 in Chinese and 5 in English) with a total of 379 pairs of samples were collected. A Meta-analysis was used to comprehensively analyze the effects of foliar Se application on the yield, grain protein, and Se content of winter wheat, and a subgroup analysis was used to evaluate the effects of different factors on response of winter wheat to foliar Se application, with no Se application as the control group and foliar Se application as the experimental group. The results showed that compared with no Se application, the yield, grain protein, and Se contents of winter wheat were increased by foliar Se application, with incremental rates of 3.80%, 2.44%, and 764.56%, respectively. In terms of the different regions, the effect of foliar Se application on yield and quality improvement was greater in the east and south than in the west and north, respectively. Overall, the effect of grain Se enrichment gradually decreased from west to east. In terms of foliar Se application management factors, it was most worthwhile to apply 15−60 g·hm⁻² once at the early filling stage or twice at the boot stage and early filling stage, which would meet the standard of Se enrichment and human needs. Soil fertility was an important factor influencing the effect of foliar Se application on the yield and quality of winter wheat. Soil contents of Se and total N had a significant effect on yield-increasing effect of foliar Se application. The effect of foliar Se application on yield improvement was the highest when the Se content of soil was between 0.2–0.4 mg·kg⁻¹. The effect of foliar Se application on winter wheat yield decreased with increasing total soil N. Soil Se, total N, available P, and available K contents significantly affected the effects of foliar Se application on protein content. The effect of foliar Se application on grain protein was higher when the soil Se content was between 0.2−0.4 mg·kg⁻¹, total N>1.5 g·kg⁻¹, available P>20 mg·kg⁻¹, and available K=100−200 mg·kg⁻¹. Soil fertility (soil Se content, organic matter content, and available K content) was the main factor affecting Se accumulation in grain when Se fertilizer was applied to the foliar. When the soil organic matter and available K contents were enhanced, foliar Se application had significantly increased the Se accumulation; however, the effect of Se accumulation caused by foliar Se application was high in Se-poor soil (<0.2 mg·kg⁻¹). Therefore, foliar Se application measures and soil conditions for optimization in different regions not only synergistically achieve the goals of high yields, good quality, and Se accumulation standards of wheat, but also reduce environmental contamination, which provides support for sustainable wheat production management with Se enrichment.