The southeastern Tibetan Plateau and surrounding areas comprise a typical tectonic belt in mainland China, characterized by a complex geological background and intense tectonic activity. We study present-day crustal deformation characteristics of this region based on GPS data for the periods 1999–2007 and 2009–2011. We first analyze the variations in crustal motion and strain rate, and then discuss the 3D crustal motion and local sub-block activities, as well as the correlation between the intensity of crustal activity and the strain rate distribution. Finally, we explain the present-day geodynamic characteristics of the region. Our results indicate that the entire region shows overall clockwise motion with respect to the stable Eurasian Plate. The tectonic boundary belts between this region and the South China Block display significant compressional strain, accompanied by associated extensional strain. Relatively high maximum shear strain and the transition zones of the significant plane strain gradients are also mainly concentrated along the Ganzi–Yushu–Xianshuihe, Anninghe–Zemuhe–Xiaojiang, Lijiang–Xiaojinhe, and Red River faults, as well as the western and southern Yunnan Province. 3D crustal velocities further reflect significant differences in tectonic activity between different structural belts. We conclude that the regions showing higher shear strain and the transition zones of the significant plane strain gradients correspond to the areas with frequent earthquakes. According to the crustal deformation and strain characteristics, we infer that the present-day geodynamic setting of the region is related to the ongoing India–Eurasia collision and the associated resistance of the stable Alashan, Ordos, and South China blocks, resulting in the extrusion of the southeastern Tibetan Plateau crustal material with an overall clockwise flow around the Eastern Himalayas and significant compressional strain along the tectonic boundary belts. Furthermore, notable compressional strain and enhanced sub-block motions occurred around the Longmenshan fault area following the Wenchuan earthquake.