Spatiotemporal changes in the surface area of inland water bodies have important implications in regional water resources, flood control, and drought hazard prediction. Although inland water bodies have been investigated intensively, few studies have looked at the effect of human activities and climate variability on surface area of inland waters at a larger scale over time and space. In this study, we used MODIS (MOD13Q1) images to determine water surface area extent at 250 m spatial resolution. We then applied this algorithm with MOD13Q1 images taken at 16-day intervals from 2000 to 2018 to a large river basin in China’s northeast high latitude region with dense stream network and abundant wetlands to investigate spatiotemporal distribution and dynamics of inland water bodies. The study identified 209 ponds, lakes, and reservoirs with an average total surface area of 2080 km2 in the past 19 years. The total water surface area fluctuated largely from 942 km2 to 5169 km2, corresponding to rainfall intensity and flood. We found that the total water surface area in this high latitude river basin showed an increasing trend during the study period, while the annual precipitation amount in the river basin also had an increasing trend concurrently. Precipitation and irrigation significantly contributed to the monthly change of water surface area, which reached the highest during June and August. The increase of water surface area was significant in the lower basin floodplain region, where agricultural irrigation using groundwater for rice production has progressed. Four nationally important wetland preserves (Zhalong, Xianghai, Momoge, and Chagan Lake) in the river basin made up nearly 50% of the basin’s total water surface area, of which Zhalong, Xianghai, and Momoge are designated by The Ramsar Convention as wetland sites of international importance. Seasonally, these water bodies reached their maximal surface area in August, when both the monsoon weather and agricultural discharge prevailed. This study demonstrates that water surface area in a high latitude river basin is affected by both human activities and climate variation, implying that high latitude regions will likely experience more changes in surface water distribution as global climate change continues and agriculture becomes intensified.