The Acoculco Caldera Complex is considered a promissory hidden high-temperature geothermal system in Mexico. To support the geothermal prospection of this anomalous area, a comprehensive programme of soil CO2 flux measurements was performed. A long-term measurement programme was conducted to determine the baseline of natural soil CO2 effluxes. Significant efforts were devoted both to measuring the CO2 fluxes between 2015 and 2022 and interpreting their origin. A comprehensive database was created using statistical and geostatistical methods to study the geochemical features of these soil CO2 fluxes. This study allows the spatial distribution and the total CO2 efflux to be quantified. Eighteen soil gas surveys of CO2 were carried out by using the accumulation chamber method. >1200 diffuse CO2 fluxes were measured in six different areas of the Acoculco Caldera. Two areas (Los Azufres and Alcaparrosa) exhibited cold degassing sites, acid-sulphate springs, and gas bubbling in surface water bodies. In contrast, other areas were related to grassland and pine forest sites. Using the graphical statistical approach (GSA) and the sequential Gaussian simulation (SGS), three degassing groups were identified. These soil CO2 fluxes were classified as high (group A), intermediate (group B), and low gas emissions (group C). The soil CO2 fluxes ranged from 1 to 26,000 g m−2 d−1, whereas lower fluxes <29 g m−2 d−1 were determined as the degassing baseline. A total CO2 flux of 492 t d−1 km−1 was estimated for the Acoculco Caldera using an integrated SGS-GSA approach, where the highest total soil CO2 fluxes were obtained for Alcaparrosa (299 t d−1 km−2) compared with Los Azufres (164 t d−1 km−2), and Surroundings (29 t d−1 km−2). Such results agree well with those values measured in other worldwide volcanic and active geothermal ecosystems. The range of CO2 isotopic composition values from −28.83 ‰ to −3.11 ‰, together with their statistical distribution, suggests multiple CO2 production sources feeding soil degassing. The combined interpretation of flux and isotopic data allowed us to identify two distinct gas sources: hydrothermal and biogenic. The composition in δ13CCO2 with the highest soil CO2 effluxes indicates a magmatic source with values of δ13CCO2 between −5.36 ‰ and −3.11 ‰. The CO2 from biogenic sources and low CO2 effluxes is characterised by values of δ13CCO2 between −28.83 ‰ to −15.77 ‰, both in the range of the typical values for biological CO2 soil degassing. The present study highlights the importance of using soil CO2 monitoring to determine baseline emissions at the early exploration stage of geothermal systems.