Core Ideas Natural source zone depletion rate spatial variability aligns with historical release areas. The sitewide average NSZD rate is adequately characterized with radiocarbon correction. NSZD rate temporal variability correlates with air temperature and precipitation. Dynamic closed chambers, concentration gradient method, and CO2 traps show discrepancies. Discrepancies in methods are related to parameter sensitivity, measurement time frame, and radiocarbon sampling. Understanding the implications of vadose zone processes across spatial and temporal scales is challenging. At petroleum release sites, biodegradation of hydrocarbon compounds contributes to biogeochemical cycling through natural source zone depletion (NSZD). Considerable gaps remain in characterization at large sites. An evaluation of NSZD rates at a >80‐ha decommissioned oil refinery was conducted using a dynamic closed chamber (DCC). Across the site, we characterized spatial variability and compared radiocarbon (14C) and background‐corrected NSZD rate estimates. At a high‐resolution (0.5‐ha) area, temporal variability in NSZD rate estimates was characterized and a method comparison was conducted for DCC, the concentration gradient method (CGM), and CO2 traps. The spatial variability of sitewide NSZD rates was significantly different from smear zone thickness, suggesting that additonal factors affect NSZD variability at a sitewide scale. The estimated sitewide average NSZD rate using the location‐specific 14C correction was significantly different from the average by the background correction method (1.2 vs. 3.0 μmol CO2 m−2 s−1, respectively). In the high‐resolution area, NSZD rates estimated by DCC varied temporally across seasonal and daily time scales. Higher temperatures were correlated with increased NSZD, and precipitation was important in dampening effluxes following rain events. The method comparison identified high sensitivity of the CGM vs. the other methods to input parameters, while CO2 traps showed relatively high intersample variability. Possible limitations to DCC, including measurement timeframe and 14C sampling method, were considered. The findings assist in setting NSZD expectations at other large sites.