Under the synergetic effect of land use and climate change, natural disasters occur frequently in the karst region of southwest China. This study used the daily precipitation data from 33 meteorological stations across 61 years (1960–2020), utilized the MK test and the Z index to calculate the levels of drought and waterlogging (DW) at multiple times (month and year) and spatial (province, sub-divisions, station) scales, and investigated the spatiotemporal patterns and their associated factors in DW in the karst mountains of Guizhou, southwest China. The results showed that: (1) DW occurred frequently and increasingly during the study period in Guizhou, with seven mutations of annual DW. (2) There were more droughts (especially heavy droughts) based on annual data, but more waterlogging (especially heavy waterlogging) based on monthly data. Drought occurred most frequently in summer, while waterlogging was most frequent in spring, followed by winter. (3) The normalized difference drought and waterlogging index (NDDWI) was created in this study to exhibit combined DW phenomena, which could be improved in the future to better present the compound hazards. The spatiotemporal patterns of DW in Guizhou were complicated and associated with terrain, geology, climate change, vegetation, land use, etc.