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<p>Carbon fluxes from agroecosystems contribute to the variability of the carbon cycle and atmospheric [CO<span class="inline-formula">₂</span>]. This study is a follow-up to Gahlot et al. (2020), which used the Integrated Science Assessment Model (ISAM) to examine spring wheat production and its drivers. In this study, we look at the carbon fluxes and their drivers. ISAM was calibrated and validated against the crop phenology at the IARI wheat experimental site in Gahlot et al. (2020). We extended the validation of the model on a regional scale by comparing modeled leaf area index (LAI) and yield against site-scale observations and regional datasets. Later, ISAM-simulated carbon fluxes were validated against an experimental spring wheat site at IARI for the growing season of 2013–2014. Additionally, we compared with the published carbon flux data and found that ISAM captures the seasonality well. Following that, regional-scale runs were performed. The results revealed that fluxes vary significantly across regions, primarily owing to differences in planting dates. During the study period, all fluxes showed statistically significant increasing trends (<span class="inline-formula"><i>p</i><i>&lt;</i>0.1</span>). Gross primary production (GPP), net primary production (NPP), autotrophic respiration (<span class="inline-formula"><i>R</i>_a</span>), and heterotrophic respiration (<span class="inline-formula"><i>R</i>_h</span>) increased at 1.272, 0.945, 0.579, 0.328, and 0.366 TgC yr<span class="inline-formula">⁻²</span>, respectively. Numerical experiments were conducted to investigate how natural forcings such as changing temperature and [CO<span class="inline-formula">₂</span>] levels as well as agricultural management practices such as nitrogen fertilization and water availability could contribute to the rising trends. The experiments revealed that increasing [CO<span class="inline-formula">₂</span>], nitrogen fertilization, and irrigation water contributed to increased carbon fluxes, with nitrogen fertilization having the most significant effect.</p>