Spatially explicit modeling techniques recently emerged as an alternative to monitor land use changes. This study adopted the well-known CLUE-S (Conversion of Land Use and its Effects at Small regional extent) model to analyze the spatio-temporal land use changes in a hot-spot in Northeast China (NEC). In total, 13 driving factors were selected to statistically analyze the spatial relationships between biophysical and socioeconomic factors and individual land use types. These relationships were then used to simulate land use dynamic changes during 1980–2010 at a 1 km spatial resolution, and to capture the overall land use change patterns. The obtained results indicate that increases in cropland area in NEC were mainly distributed in the Sanjiang Plain and the Songnen Plain during 1980–2000, with a small reduction between 2000 and 2010. An opposite pattern was identified for changes in forest areas. Forest decreases were mainly distributed in the Khingan Mountains and the Changbai Mountains between 1980 and 2000, with a slight increase during 2000–2010. The urban areas have expanded to occupy surrounding croplands and grasslands, particularly after the year 2000. More attention is needed on the newly gained croplands, which have largely replaced wetlands in the Sanjiang Plain over the last decade. Land use change patterns identified here should be considered in future policy making so as to strengthen local eco-environmental security.