In order to implement optimal farming practices for increasing soil organic carbon (SOC) in agro-ecosystems, there is a need for understanding how management practices and climate change alter SOC levels. This study quantified the influence of agricultural management practices and climatic factors on SOC changes in Eastern China’s upland-crop fields in northern Jiangsu Province for the period of 2010–2039, by using the DeNitrification-DeComposition (DNDC, version 9.5) model. We utilized the currently most detailed soil database, which is at a scale of 1:50,000, containing 17,024 soil polygons derived from 983 upland soil profiles. Across all the examined scenarios of agricultural management practices, our results show that the carbon sequestration potential in the upper layer soil (0–50cm) of the study area varied from 6.93 to 155.11Tg C during 2010–2039, with an average rate of 59 to 1317kg C ha−1 year−1. As a promising alternative, the combined scenario of crop residue return rate of 50% and farmyard manure incorporation rate of 50% is recommended for agricultural management practice in this region. Meanwhile, climate conditions play a significant role in the annual SOC changes as well. Air temperature increase of 2–4°C leads to 3.41–7.51Tg C decrease in SOC under conventional management for the entire study region. Decreasing or increasing precipitation by 20% would increase 0.57 Tg C or decrease 1.09Tg C under the conventional management scenario, respectively. Additionally, among all the soil groups, the fluvo-aquic soils have the highest C sequestration rate in most scenarios. Our findings could be used to inform optimal agricultural management toward climate mitigation.