Postharvest quality deterioration and pathogenic infestation interfere with the development of the pear industry. Nitric oxide (NO), as an emerging potential postharvest fruit protectant, can simultaneously stop fruit senescence and improve disease resistance. Global visualization of NO in the pears postharvest process is necessary. In this study, NO gas was used to fumigate 'Korla' fragrant pear, we explored changes in phenotypic indicators and gene expression of pear fruit during 120 d of refrigeration and 15 d of Alternaria sp. infection. Similar to 1-MCP treatment, NO treatment hindered the deterioration of pear quality, reduced and delayed the respiration and ethylene release rates, increased the contents of major quality traits and nutrients, and downregulated many carbohydrate metabolism genes. NO reduced Alternaria sp. damage, activated the activity of resistance enzymes of infected pears, and increased the contents of antioxidant substances. A large number of induced systemic resistance genes were upregulated in infected pears. Pear cuticular wax biosynthesis responded to NO treatment with increased total wax content and upregulation of the core genes ECERIFERUM (CER) and 3-KETOACYL-COA SYNTHASE (KCS). These results provide guidance for the application of NO in fruit postharvest.