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At present, the role of agricultural practices on the dynamic of GHGs is being investigated worldwide. In this study, the effects of soil tillage practices (conventional vs. conservation techniques) and fertilization sources (inorganic vs. organic) on soil CO2 emissions in durum wheat (Triticum durum Desf.)–potato (Solanum tuberosum L.) rotation in the Mediterranean area were evaluated. This study aimed to understand the changes in the soil carbon content and the soil CO2 emissions under different soil tillage practices (moldboard plow (P), subsoiler (R), and spading machine (S)) and fertilization sources (mineral (M) and organic (O) with municipal organic waste). Soil CO2 flux, soil water content, and soil temperature data were collected for both crops using a portable closed-chamber infrared gas dynamics system. Significant relationships were detected between soil CO2 emissions and soil temperate and soil water content. However, these relationships were found only for durum wheat crops. Our findings indicate that including sustainable agricultural practices in wheat–potato rotation system could act as an appropriate alternative option to increase soil organic carbon, mitigate CO2 emissions, and reduce the dependence on chemical inputs and energy.