As one of the promising candidates for developing next-generation structural materials, high-entropy alloys (HEAs) have recently attracted significant interest because of their unique mechanical properties, including their coexisting of high strength and ductility properties. Here, through atomic simulations, we demonstrate that the segregation of elements to grain boundaries (GBs) due to atomic-size differences, which is one of the most important characteristics of HEAs, contributes to the coexistence of high strength and high ductility in HEAs. To focus on only the effect of the size difference on the GB segregation, ignoring the difference in the chemical bonding energies among all the constituent elements, we employ two-dimensional virtual quinary HEA models. The HEAs are subjected to tensile and compressive load tests, and the stress required for dislocation emission from the GBs is measured. We demonstrate that the GB segregation in the HEAs increases the stress required for dislocation emission from the GBs, thereby increasing the strength of the HEAs. This is because the GB segregation in the HEAs stabilizes the GB structure by decreasing the GB free volume. Notably, the GB segregation also decreases the heterogeneity of the mechanical field between the grain interiors and the GBs, which is an intrinsic attribute of ordinary materials, and the homogenization of the mechanical field can improve the ductility of HEAs, preventing intergranular fracture. Our results can serve as a guide for designing HEAs with both high strength and high ductility through the effective utilization of GB segregation.