Abstract: Based on a long-term field experiment at the Huanjiang observation and research station for karst ecosystems of the Chinese Academy of Sciences in Guangxi, six fertilization treatments were established, including no fertilization (CK), chemical fertilizer alone (NPK), and four combined organic and inorganic fertilization treatments: straw returning plus NPK (STNPK), cattle manure plus NPK (MNPK), filter mud plus NPK (SLNPK), and sugarcane ash plus NPK (BANPK). This study investigated the characteristics of soil carbon and nitrogen nutrients and extracellular enzyme activities in the rhizosphere and bulk soils of maize under different fertilization regimes. The results showed that combined organic and inorganic fertilization generally increased soil organic carbon (SOC) and total nitrogen (TN) contents. Compared with CK, the BANPK treatment significantly increased rhizosphere SOC by 19.4%, while the MNPK treatment significantly increased rhizosphere TN by 11.3%. In contrast, the NPK treatment significantly decreased rhizosphere SOC by 11.4% (P < 0.05). The activity of N-acetyl-β-D-glucosaminidase (NAG) was significantly higher in the rhizosphere than in the bulk soil, whereas no significant rhizosphere effects were observed for β-glucosidase (BG) or leucine aminopeptidase (LAP) activities (P > 0.05). Two-way analysis of variance showed that fertilization treatment significantly affected only BG activity, whereas soil position significantly influenced only NAG activity. Correlation and multivariate analyses further indicated that β-xylosidase (BX), the microbial biomass carbon to microbial biomass nitrogen ratio (MBC/MBN), and NAG contributed most to the overall variation in soil properties, indicating that these variables effectively characterize changes in soil nutrient status and microbial functions under different fertilization regimes. Extracellular enzyme activities in the bulk soil were generally positively correlated with nutrient indicators, whereas NAG activity showed a negative, although non-significant, correlation with dissolved organic carbon (DOC) in the rhizosphere. Overall, long-term combined organic and inorganic fertilization improved soil carbon and nitrogen nutrient status in karst croplands, with the MNPK and BANPK treatments showing relatively superior performance. However, the effects of different fertilization regimes on extracellular enzyme activities and microbial functions were selective, and the underlying mechanisms require further verification through observations across multiple crop growth stages combined with more comprehensive microbial indicators.