Ecosystem water use efficiency (WUE) and carbon use efficiency (CUE), as two of the most important ecological indicators of an ecosystem, represent the carbon assimilation rate of unit water consumption and the capacity of transferring carbon from the atmosphere to potential carbon sinks. Revealing WUE and CUE changes and their impact factors is vital for regional carbon-water interactions and carbon budget assessment. Climate affects carbon and water processes differently. Compared to WUE, the variations in CUE in response to climate factors and human activity remain inadequately understood. In this study, ecosystemlevel WUE and CUE variations in the Songnen Plain (SNP), Northeast China, during 2001-2015, were investigated using Moderate Resolution Imaging Spectroradiometer (MODIS) satellite data. e relationships between WUE, CUE, main climate factors, and human impacts were explored. e results showed that ecosystem WUE and CUE have fluctuated over time, with regional average values of 1.319 gC·kg −1 H 2 O and 0.516, respectively. Deciduous broad-leaved forests had the highest average WUE but the lowest CUE. e multiyear average CUE of grassland ranked in first place, while the lowest WUE indicated that a lesser capacity of net productivity was generated by the use of limited water supply. WUE and CUE showed a downward trend in most areas of the SNP, indicating that the carbon sequestration capacity of the terrestrial ecosystem became weaker in the past 15 years. Annual precipitation and relative humidity had positive influences on WUE and CUE in more than 60% of the study area. e total annual sunshine duration and annual average temperature negatively affected WUE and CUE in most areas. Human activities had a positive effect on ecosystem WUE changes in the SNP but might inhibit CUE variations. Our findings aid in understanding the biological regulation mechanisms of carbon-water cycle coupling and provide a scientific basis for formulating sustainable regional development strategies and guiding water and land resources management.