Plant tissues and cells can sense and transmit stress signals, change their morphological structures, alter protein and gene expression, and activate metabolic pathways to adapt to stressful environments. However, the internal and external resistance mechanisms related to antioxidation in local tissues or cells suffering from biotic stress remain unclear. We studied the response of Malus crabapple leaves to cedar-apple rust infection, and the results revealed that significant color changes and flavonoid compound accumulation (especially anthocyanins) occurred in the rust-infected tissue (RIT), whereas no significant color changes and only flavonol and flavanone accumulation occurred in the non-infected tissue (NIT). There was an up-regulation of expression of the key structural genes and MYBs related to anthocyanins biosynthesis in the RIT, while its expression related to flavonol and flavanone biosynthesis was up-regulated in the NIT. Moreover, the accumulation of glucose, sucrose, and sorbitol among the tested carbohydrates was successively induced at higher levels in the RIT and NIT. Importantly, rust infection increased the contents of jasmonate (JA), abscisic acid (ABA), and ethylene (ETH), and significantly up-regulated related key genes in the RIT and NIT during rust spot expansion. Spearman’s correlation and redundancy analyses indicated that ABA and ETH were potentially involved in oxidative defense responses to rust spot expansion by initiating the transcription of key genes, increasing the sugar supply, and adjusting the osmotic balance.