Understanding the influence of grazing management and environmental drivers on net ecosystem exchange of CO2 (NEE) is essential for optimizing carbon (C) uptake in rangelands. Herein, using 15 treatment-years (two 3-yr experiments, one with three grazing treatments, the other two) and Bowen ratio flux towers, we evaluated the influence of grazing intensity, soil water content (SWC), and plant cover (Normalized Difference Vegetation Index, or NDVI) on NEE in Colorado shortgrass steppe. Among several soil water and plant cover traits evaluated over 6-yr, early season (April, DOY 91–120) SWC and early season (DOY 130) NDVI weremost highly correlated with NEE (-0.96 and-0.98, respectively) during the second quarter (April to June) of the year and also over the entire growing season (April to September;-0.97 and-0.96). Due to the strong effect of early-season SWC, an average of 166 gm-2 CO2 were lost in 2 yr with dry spring weather, compared with an average annual uptake of 218 g m-2 CO2 in 4 yr with more abundant early-season precipitation and plant cover. Grazing effects on NEE were also apparent. In one experiment, moderate grazing resulted in annual CO2 uptake of 267 g m-2 CO2 over 3 yr compared with essentially zero NEE in heavily grazed pasture. However, that treatment difference in annual NEEwas only half that experienced between dry and wet years. Similar trends were observed in a second experiment, although results were insignificant. Results suggest that the recommended moderate grazing intensity for the Colorado shortgrass steppe is near optimal for CO2 uptake under season-long continuous grazing, with annual climatic variability sometimes being more influential. To enhance C sequestration in the western Great Plains of North America, grazing management strategies should emphasize flexible and adaptive practices that consider early-season SWC and promote vegetation cover during the key early spring growth period.