AbstractAverage maize yield per hectare has increased significantly because of the improvement in high‐density tolerance, but little attention has been paid to the genetic mechanism of grain yield response to high planting density. Here, we used a population of 301 recombinant inbred lines (RILs) derived from the cross YE478 × 08–641 to detect quantitative trait loci (QTLs) for 16 yield‐related traits under two planting densities (57,000 and 114,000 plants per ha) across four environments. These yield‐related traits responded differently to high‐density stress. A total of 110 QTLs were observed for these traits: 33 QTLs only under low planting density, 50 QTLs under high planting density and 27 QTLs across both densities. Only two major QTLs, qCD6 and qWKEL2‐2, were identified across low‐ and high‐density treatments. Seven environmentally stable QTLs were also observed containing qED6, qWKEL3, qRN3‐3, qRN7‐2, qRN9‐2 and qRN10 across both densities, as well as qRN9‐1 under low density. In addition, 16 and eight pairs of loci with epistasis interaction (EPI) were detected under low and high planting densities, respectively. Additionally, nine and 17 loci showed QTL × environment interaction (QEI) under low‐ and high‐density conditions, respectively. These interactions are of lesser importance than the main QTL effects. We also observed 26 pleiotropic QTL clusters, and the hotspot region 3.08 concentrated nine QTLs, suggesting its great importance for maize yield. These findings suggested that multiple minor QTLs, loci with EPI and QEI, pleiotropy and the complex network of “crosstalk” among them for yield‐related traits were greatly influenced by plant density, which increases our understanding of the genetic mechanism of yield‐related traits for high‐density tolerance.