The climate in Southwest China are predominantly under the influences of three contrasting climate systems, namely the East Asian monsoon, the South Asian monsoon, and the westerlies. However, it is unclear if the diversified climate systems, in combination with the complex terrain and varying vegetation types, would result in contrasting patterns of changes in climate across the region. Based on the CRU TS data for the period 1901−2017, we examined the spatiotemporal characteristics of the regional climate, and identified types of climate change patterns and drivers. Overall, the region experienced significant increases in annual mean temperature during 1901−2017, with occurrence of a significant turning point in 1954 for a more pronounced warming (0.16 °C/10 a). The annual precipitation fluctuated greatly over the study period without apparent trend, albeit the occurrence of a significant turning point in 1928 for a slight increase in the later period (1.19 mm/10 a). Spatially the multi-year averages of selective climate variables during 1901–2017 displayed a trend of decreases from southeast to northwest, but with increasing variability. We identified five major climate change types across the study region, including warmer (T+), drier (P−), warmer-drier (T+P−), warmer-wetter (T+P+), and no significant changes (NSC). The type T+P+ mainly occurred in the western parts over the plateau sub-frigid semiarid ecozone (77.0%) and the plateau sub-frigid semihumid ecozone (19.9%). The central parts of the region are characterized by the type T+, corresponding to six ecozones, including the mid-subtropical humid ecozone (33.1%), the plateau temperate humid-semihumid ecozone (28.8%), the plateau sub-rigid semihumid ecozone (9.5%), the southern subtropical humid ecozone (8.1%), the plateau sub-frigid arid ecozone (7.3%), and the plateau temperate semiarid ecozone (6.6%). No significant change in climate was detected for the eastern parts over the mid-subtropical humid ecozone (67.3%), the plateau temperate humid and semihumid ecozone (19.5%) and the plateau sub-frigid semihumid ecozone (8.8%). The types P− and T+P− together accounted for less than 5% of the entire study region, which predominantly occurred in central Yunnan-Guizhou Plateau and south of the southeastern Xizang, corresponding predominantly to the mid-subtropical humid ecozone. Across the region and within the zonal climate change types, vegetation and topography both played a significant role in determining the climate variability and magnitude of changes. Our results suggest that the southwestern China experienced intensified influences of the southeasterly monsoon and the southerly monsoon in the regional climate, while the westerly alpine influences subsided; topography and vegetation affected the magnitudes of the directional changes in climate at a local scale.