To investigate the protective effect of quercetin against hypertensive renal damage through the "energy-fibrosis-senescence" pathway. Network pharmacology was employed to predict the common targets between quercetin and hypertensive renal damage, followed by KEGG pathway enrichment analysis. Wistar Kyoto (WKY) rats were set as the control group, and spontaneously hypertensive rats were randomly divided into the model group, low-dose quercetin group (2.5 mg/kg), and high-dose quercetin group (10 mg/kg). The control group and model group were given methylcellulose by gavage. After four consecutive weeks of gavage, rat renal tissue samples were collected for HE staining, Masson staining, and PAS staining. A cellular model was established by stimulating NRK-52E cells with angiotensin II (Ang II), and experiments including CCK-8, immunofluorescence, flow cytometry, and Western blot were performed for verification. Results from network pharmacology suggested that the adenosine 5'-monophosphate-activated protein kinase (AMPK) signaling pathway may play an important role in the improvement of hypertensive renal damage by quercetin. In vivo experiments showed that quercetin effectively reduced blood pressure, alleviated pathological changes in renal structure, and mitigated renal damage. In vitro experiments revealed that quercetin activated AMPK and its downstream silent information regulator 1 (SIRT1), increased cellular adenosine triphosphate (ATP) content, reduced the decline in mitochondrial membrane potential, decreased the expression level of reactive oxygen species (ROS), and maintained the homeostasis of mitochondrial energy metabolism. Additionally, quercetin downregulated the expression of mesenchymal marker α-smooth muscle actin (α-SMA), upregulated the expression of epithelial marker E-cadherin, and reduced the expression of fibrotic markers Collagen I and transforming growth factor-beta 1 (TGF-β1), thereby inhibiting the epithelial-mesenchymal transition process and improving fibrosis. By reducing the expression of aging markers, tumor protein P53 and the cyclin-dependent kinase inhibitor 2A (CDKN2A/P16), the aging process is intervened. In summary, quercetin can alleviate hypertensive renal damage, and activating the AMPK/SIRT1 pathway through the "energy-fibrosis-aging" axis may be its potential mechanism.