Moisture is the most important environmental factor limiting seed regeneration of shrubs in desert areas. Therefore, understanding the effects of moisture changes on seed germination, morphological and physiological traits of shrubs is essential for vegetation restoration in desert areas. In March to June 2023, in a greenhouse using the potting method, we tested the effects of soil moisture changes (5%, 10%, 15%, 20% and 25%) on seed germination and seedling growth of six desert shrubs (Zygophyllum xanthoxylum, Nitraria sibirica, Calligonum mongolicum, Corethrodendron scoparium, Caragana korshinskii, and Corethrodendron fruticosu). Results showed that (1) seed germination percent and vigor index were significantly higher at 15 and 20% soil moisture content than at 5 and 10%; (2) shoot length, primary root length, specific leaf area and biomass of seedlings were significantly higher in the 15% and 20% soil moisture content treatments than in the 5% and 10% treatments; (3) superoxide dismutase activity (SOD) and soluble protein content (SP) decreased with decreasing soil water content, while peroxidase activity (POD) and catalase activity (CAT) showed a decreasing and then increasing trend with increasing soil water content; (4) the six seeds and seedling of shrubs were ranked in order of their survivability in response to changes in soil moisture: Caragana korshinskii > Zygophyllum xanthoxylum > Calligonum mongolicum > Corethrodendron scoparium > Corethrodendron fruticosu > Nitraria sibirica. Our study shows that shrub seedlings respond to water changes by regulating morphological and physiological traits together. More importantly, we found that C. korshinskii, Z. xanthoxylum and C. mongolicum were more survivable when coping with water deficit or extreme precipitation. The results of the study may provide a reference for the selection and cultivation of similar shrubs in desert areas under frequent extreme droughts in the future.