Climate variability, soil type, land use, and vegetation structure modulate soil organic carbon (SOC) dynamics, but their effects on sensitive soil carbon indicators are not adequately quantified in semi-arid ecosystems. This research examined the independent and synergistic impacts of pedo-climate, land use, and canopy cover on permanganate oxidizable carbon (POXC), soil microbial respiration (CO2-C), and the carbon mineralization rate (CMR) in the semi-arid regions of West Africa to determine their effectiveness as indicators of soil carbon dynamics. We collected 480 composite soil samples across Sudanian and Sudano-Sahelian zones, covering three land use types (cropland, fallow, protected area), two canopy positions (subcanopy, intercanopy), and two depths (0-10 cm, 10-30 cm). POXC, CO2-C, and SOC concentrations were analyzed, and CMR was derived from CO2-C per unit SOC. The indicators exhibited distinct sensitivities, with POXC responding primarily to pedo-climate and canopy cover. CO2-C was influenced by all factors with depth-amplified variation, and CMR was most sensitive to land use and canopy position in topsoil but shifted to pedo-climatic control at depth. The fixed effects explained a small portion (14% to 16%) of topsoil (0-10 cm) variance, indicating significant unmeasured variability sources. Depth-moderated indicator relationships, POXC-SOC correlations weakened with depth, whereas CO2-C-CMR associations strengthened, indicating a transition from surface labile carbon control to deeper microbial and nutrient constraints. Critically, the indicators provide complementary, depth-explicit information; POXC and SOC contextualize pool size and labile availability, whereas CO2-C and CMR assess the functional accessibility and energetic feasibility of decomposition. Therefore, these metrics are best used jointly to signal early changes rather than as stand-alone indicators. Future work should identify additional drivers to enhance capacity across depths and contexts.