Giant reed (Arundo donax L.) has great potential for phytoremediation of N balance-disrupted soils due to its large plant biomass production and strong N use efficiency. Soil properties and the artificial modification in agricultural production cause a heterogeneous distribution of N. However, little is known about the differential responses of A. donax at varying N abundances. Herein, giant reed seedlings were grown in solutions with low, moderate and high N supply under hydroponic culture system. We found that both nonoptimal N inhibited the growth and biomass accumulation of A. donax, which was severely repressed by high N. While phytophysiological assays showed that N stress decreased photosynthetic rate and Fv/Fm by increasing reactive oxygen species (ROS) accumulation and lipid peroxidation, the activity of antioxidant enzymes and redox poise in leaves and roots was promoted to minimize excessive ROS accumulation and oxidative stress. High-throughput transcriptomic profiling revealed a total of 19,848 and 16,736 differentially expressed genes (DEGs) under low N and high N conditions, respectively. Based on the results of DEG function annotation and enrichment analyses, varying N abundances up-regulated the expression of a number of genes involved in ROS production and antioxidant defense systems and down-regulated most genes related to photosynthesis, which may contribute to plant response. The expression of 76 and 64 transcription factors (TFs) in leaves, 88 and 110 TFs in roots were up-regulated under low N and high N conditions, respectively, which may contribute to alleviating damage caused by varying N treatment. Our findings would enrich our understanding of the growth and development changes of A. donax plants under low N or high N conditions, and might also provide suitable gene resources and important implications for the genetic improvement of plant N resistance and accumulation through molecular engineering of these genes under varying N abundances in soils.