【Objective】This study aimed to systematically investigate the effects of long-term fertilization regimes on the maize rhizosphere soil chemical properties, enzyme activities, and bacterial community structure in upland red soil. Furthermore, it sought to elucidate the relationships between key differential bacterial taxa, rhizosphere nutrient status, and enzyme activities, thereby providing a theoretical basis for scientific fertilization and soil health management in the red soil regions of southern China.【Methods】Based on a 40-year long-term field fertilization experiment, three treatments were established: no fertilization (CK), chemical fertilization (NPK), and combined organic and inorganic fertilization (NPKM). High-throughput 16S rRNA sequencing was employed to characterize the rhizosphere bacterial community and identify key differential taxa. Meanwhile, soil pH, nutrient contents, and the activities of extracellular enzymes involved in carbon (C), nitrogen (N), and phosphorus (P) cycling were determined【Results】Long-term application of chemical fertilizer alone aggravated rhizosphere soil acidification and reduced nutrient availability. In contrast, combined organic and inorganic fertilization effectively alleviated soil acidification, significantly increased soil organic matter (SOM), available nitrogen (AN), and available phosphorus (AP), and enhanced the activities of β-glucosidase (BG), leucine aminopeptidase (LAP), β-N-acetylglucosaminidase (NAG), and alkaline phosphatase (ALP). Moreover, NPKM treatment markedly increased bacterial α-diversity, optimized community structure, and enriched key functional taxa such as Gemmatimonadaceae, Nitrosomonadaceae, Pyrinomonadaceae, Roseiflexaceae, and Vicinamibacteraceae, whose abundances were positively correlated with soil pH, nutrient contents, and enzyme activities.【Conclusion】Long-term combined organic-inorganic fertilization improves rhizosphere nutrient status, enhances the activities of enzymes related to carbon, nitrogen, and phosphorus cycling, and optimizes microbial community structure. These synergistic effects collectively promote nutrient cycling and ecological functioning in the rhizosphere, providing a scientific basis for improving soil fertility and advancing sustainable agricultural production in acidic red soil regions.