To better determine how gamma irradiation (GI) improves abiotic stress resistance, a transcriptome analysis of postharvest L. edodes in response to 1.0 kGy GI was conducted, and further the underlying mechanism of GI in delaying quality deterioration over 20 d of cold storage was explored. The results suggested that GI was involved in multiple metabolic processes in irradiated postharvest L. edodes. In comparison with the control group, the GI group contained 430 differentially expressed genes, including 151 upregulated genes and 279 downregulated genes, which unveiled characteristic expression profiles and pathways. The genes involved in the pentose phosphate pathway were mainly upregulated and the expression level of the gene encoding deoxy-D-gluconate 3-dehydrogenase was 9.151-fold higher. In contrast, the genes related to other energy metabolism pathways were downregulated. Concurrently, GI inhibited the expression of genes associated with delta 9-fatty acid desaturase, ribosomes, and HSP20; thus, GI helped postpone the degradation of lipid components, suppress transcriptional metabolism and regulate the stress response. Additionally, the metabolic behavior of DNA repair induced by GI intensified by noticeable upregulation. These regulatory effects could play a potential and nonnegligible role in delaying the deterioration of L. edodes quality. The results provide new information on the regulatory mechanism of postharvest L. edodes when subjected to 1.0 kGy GI during cold storage.