The agricultural sector is the most important economic component in Afghanistan, as 80% of the population is involved. The improvement of cereal production is an urgent task to meet the nation’s demand for the staple within the limited arable land. To promote a sustainable crop production system, this study examined the soil quality to learn the basic knowledge of soil fertility and the environmental impact of different rice–wheat cropping systems in Khost, Afghanistan by using the life cycle assessment (LCA) method. The economic analysis of each farming system was conducted by the data gathered by the farmers’ interviews along with LCA data collection. The analysis considered the on-farm activities, which were required to produce 1 kg of wheat and rice. It included energy use, production, and farming inputs such as fertilizer and agrochemicals. Conventional farming with organic fertilizer application (CF+OF) was compared with conventional farming (CF). The LCA results showed the total greenhouse gas (GHG) emission was higher in rice production compared to wheat production. However, CO2 absorption by the crops was far greater than the total GHG emission in both systems and showed great potential for soil carbon sequestration for mitigation of global warming. The soil examination revealed the CF+OF system increased soil total carbon (TC), active C (AC), total N (TN), soil organic carbon storage (SCS), P, and K+ after four years of organic fertilizer application. The yield of each crop was slightly higher in the CF system; however, the CF+OF system increased net income by reducing the cost for fertilizer. The study concluded the CF+OF system can improve soil fertility in the long term while saving the farming operation cost. Further research is required to determine the best combination of practices to improve cattle manure characteristics and farm management for soil carbon sequestration to promote a sustainable farming system in the country.