Water resources, agriculture and ecological environment of river basins are affected by global climate change to different degrees. Knowledge of the trends and spatial patterns of climate change in the Huaihe River Basin is beneficial to the formulation of the basins climate change response strategies. The spatial-temporal patterns of several key climatic factors are analyzed based on historical observations at 145 meteorological stations between 1961 and 2010 in the Huaihe River Basin. Study results suggest that, (1) There is an increasing trend in the annual average temperature of the entire basin. However, there is much spatial variability in its change. Regions with significant increase in temperature include the Nansihu region, the southern region of the Middle and Lower Huaihe River Basin, and the Funiu Mountain region. Annual maximum temperature increases slowly in the mountainous regions, while annual minimum temperature increased significantly in the regions. Annual average daily temperature range of the entire basin shows a decreasing trend. Spatially, it shows a decreasing trend in the central plains and an increasing trend in the rest areas. (2) Surface air pressure shows a decreasing trend in the entire basin with increasing spatial variability. Its central plains exhibit a slow rate of decrease, while the Tongbai and Dabie Mountain regions in the upstream exhibit a fast rate As a whole average wind speed of the entire basin shows a decreasing trend as well as its spatial variability. However, wind speed shows an increasing trend in the mountainous regions of the Upper Huaihe River Basin, the Yimeng Mountains, and the coastal Lixiahe region. (3) Relative humidity shows a weak increasing trend in the western region in contrast to a weak decreasing trend in the east. There is a significant decreasing trend in sunshine duration with more decrease in the west than in the east. (4) Annual average precipitation shows a trend of increase to the south of the main reach of the Huaihe River and decrease to the north. This leads to a further increase in the spatial variability of annual precipitation between the wet south and the dry north.