Copper (Cu) contamination in paddy fields leads to excessive Cu in rice grains and a low grain yield, posing a serious threat to sustainable agricultural production. We propose the application of seed priming with silver ions (Ag + ) as biostimulants to trigger reactive oxygen species (ROS) production and enhance immune responses, thereby improving rice resistance to Cu stress. The results showed that seed priming with 10 μM Ag + significantly improved rice tolerance to Cu, increased the fresh biomass by 22.1%, and reduced the Cu content in the roots and shoots by 25.3 and 13.4%, respectively, compared to the hydropriming treatments. Furthermore, seed priming with 10 μM Ag + increased nutrient uptake in rice, leading to higher contents of Ca (15.1%), Fe (14.9%), and Mg (10.2%) in the shoots as well as Ca (21.0%), Mn (37.0%), and Mg (29.1%) in the roots. More Cu was immobilized in the root cell wall, thereby significantly enhancing root cell viability, maintaining the root morphology, and reducing malondialdehyde accumulation. Transcriptomics analyses revealed that Ag + -priming activated the phytohormone signal transduction and mitogen-activated protein kinase (MAPK) signaling pathway and other kinase signaling pathways in rice roots under Cu stress. These signals triggered the upregulation of defense-related gene expression, including the Cu vesicle transporter gene, oxidoreductase activity genes, and hydrogen peroxide catabolic process genes, amino acid metabolism, purine metabolism, and starch and sucrose metabolism. This study suggests that seed Ag + -priming is a simple and effective way to alleviate Cu toxicity and decrease Cu accumulation in rice, which ensures safe rice production in a sustainable way.