Irrigation in loess tableland areas of northwest China has induced a large number of landslides around their edges, of which loess–red mudstone landslide is one of the most frequent types. Salt sinters commonly observed at the toes of these landslides, where the weathered red mudstone (WRM) outcrops, have raised the possibility that removal of soluble salts in the WRM by irrigation water could be crucial in the reduction of its shear strength, and thus in the occurrence of these landslides. In order to investigate the effects of lixiviation by irrigation water on residual shear strength of the WRM, samples of the WRM close to two landslides in Lanzhou city, one of the largest cities in northwest China, were tested after being treated under different conditions. These included: (1) saturation with the Yellow River water, the only source of irrigation, (2) saturation with groundwater, and (3) saturation and leaching with deionized water. Based on the results of these tests, specific mechanisms of residual shear strength reduction of the WRM due to lixiviation by irrigation water were discussed in terms of physico-chemical interactions between the WRM and water. It was found that lixiviation reduced residual shear strength and residual friction angle φr′ of the WRM by up to 65% and 62% respectively, after being leached 6 times. This coincided with a dramatic dissolution and leaching of soluble salts from the WRM. Particle size distribution showed that the more the WRM was leached, the more the clay fraction and the lesser coarser fractions. This suggested that reduction in residual shear strength of the WRM could be attributed to mainly disaggregation of particles coarser than clay, and to a lesser degree to weakening of interparticle forces among individual clays. It was further postulated that variation in clay mineralogy may influence performance of particle disaggregation.