Limited data are available on copper (Cu)–pH interaction-responsive genes and/or metabolites in plant roots. Citrus sinensis seedlings were treated with 300 μM (Cu toxicity) or 0.5 μM (control) CuCl2 at pH 3.0 or 4.8 for 17 weeks. Thereafter, gene expression and metabolite profiles were obtained using RNA-Seq and widely targeted metabolome, respectively. Additionally, several related physiological parameters were measured in roots. The results indicated that elevating the pH decreased the toxic effects of Cu on the abundances of secondary metabolites and primary metabolites in roots. This difference was related to the following several factors: (a) elevating the pH increased the capacity of Cu-toxic roots to maintain Cu homeostasis by reducing Cu uptake and Cu translocation to young leaves; (b) elevating the pH alleviated Cu toxicity-triggered oxidative damage by decreasing reactive oxygen species (ROS) formation and free fatty acid abundances and increasing the ability to detoxify ROS and maintain cell redox homeostasis in roots; and (c) increasing the pH prevented root senescence and cell wall (CW) metabolism impairments caused by Cu toxicity by lowering Cu levels in roots and root CWs, thus improving root growth. There were some differences and similarities in Cu–pH interaction-responsive genes and metabolites between leaves and roots.