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Guizhou Karst Plateau is located at the center of the karst region in Asia, where landslides are a typical disaster. Affected by the local karst environment, the landslides in this region have their own characteristics. In this study, 3975 landslide records from inventories of the Guizhou karst plateau are studied. The geographical detector method is used to detect the dominant casual factor and predominant multi-factor combinations for the local landslides. The results show that landslides are prone to areas on slopes between 10 degrees and 35 degrees, of clay rock, in close proximity to gullies, and especially in areas of moderate vegetation, dryland, and mild rocky desertification. Continuous precipitation over 10 days has a great effect on landslide occurrence. Compared with the individual factors, the impact of two-factor interaction has greater explanatory power for landslide volume. The volume of earthquake-induced landslides is predominantly controlled by the interactions of faults and slopes, while that of human-induced landslides is affected by the interactions of land cover and hydrological conditions. For rainfall-induced landslides, the dominant interactions vary in different regions. In the central karst basin, the interactions between faults and precipitation can explain over 90% of the variations in landslide volumes. In the southern hilly karst region, the interactions between lithology and slope can explain over 71% of the variations in landslide volume and those between fault and land-use can explain 50% of the variations of the landslide volumes in the northeastern mountainous karst region.