The Lancang-Mekong River Basin (LMRB) in Mainland Southeast Asia is home to~70 million people, mostly living in poverty and typically working in primary freshwater-related sectors, particularly agriculture and fishery. Understanding the mechanisms of the historical variability in precipitation (as the crucial water source) plays a key role in regional sustainable development throughout the LMRB. Herein, the spatiotemporal variability in interannual and intra-annual precipitation over the LMRB was analyzed using the Global Precipitation Climatology Centre (GPCC) data for the period 1952-2015. The empirical orthogonal function (EOF) and wavelet transform coherence methods were utilized to investigate the relationships of such historical variations in annual (water year: November-October), dry season (November-May), and wet season (June-October) precipitation with 13 different climate teleconnections (eight large-scale oceanic-atmospheric circulation patterns and five summer monsoons). On the basin scale, only a significant (p < 0.05) wetting trend in the dry season precipitation (DSP) was uncovered. Spatially, significant wetting (drying) trends in annual precipitation detected over the northeastern (most western) parts of the Mekong River Basin during the water years 1952-2015, largely contributed by the substantial increases (decreases) in historical wet season precipitation. The most important precipitation pattern (EOF1) was identified as a strong (relatively weak) positive center in the eastern (southwestern) Mekong River Basin accompanying by a significantly high (relatively low) positive value for the first EOF mode of the dry season precipitation (wet season precipitation). Precipitation variability in the LMRB was significantly associated with the South Asian Summer Monsoon Index, Southern Oscillation Index, and Indian Summer Monsoon Index. Precipitation is the most basic link between atmospheric (e.g., evaporation and cloud) and land-surface (e.g., soil moisture and infiltration) hydrological processes in the water cycle mechanism (e.g., Andersson et al., 2005). It is also considered to be one of the key hydrometeorological variables for detecting regional climatic changes around the world (e.g.,