In this study, field-grown wheat (Triticum aestivum L.) was treated with normal (Nn) and excessive (Ne) levels of fertilizer N. Results showed that Ne depressed the activity of superoxide dismutase and peroxidase and increased the accumulation of reactive oxygen species (ROS) and malondialdehyde. The normalized difference vegetation index (NDVI) was higher under Ne at anthesis and medium milk but similar at the early dough stage and significantly lower at the hard dough stage than that under Nn. The metabolomics analysis of the leaf responses to Ne during grain filling showed 99 metabolites that were different between Ne and Nn treatments, including phenolic and flavonoid compounds, amino acids, organic acids and lipids, which are primarily involved in ROS scavenging, N metabolism, heat stress adaptation and disease resistance. Organic carbon (C) and total N contents were affected by the Ne treatment, with lower C/N ratios developing after medium milk. Ultimately, grain yields decreased with Ne. Based on these data, compared with the normal N fertilizer treatment, we concluded that excessive N application decreased the ability to scavenge ROS, increased lipid peroxidation and caused significant metabolic changes disturbing N metabolism, secondary metabolism and lipid metabolism, which led to reduced grain filling in wheat.