The uneven spatial and temporal distribution of precipitation poses significant challenges to the growth and development of winter wheat. Screening drought-resistant and water-saving winter wheat varieties in water-limited regions is crucial for increasing crop production. However, quickly screening suitable cultivars remains a challenge. Utilizing unmanned aerial vehicles (UAVs) for remote sensing (RS) offers a solution by enabling the prediction of yields, overcoming issues such as the labor-intensive process of manual yield data collection and the difficulty of screening during the growing season. In this study, three types of water treatments were applied to 48 varieties screened in the North China Plain, with each water treatment repeated three times using a randomized block design. The aim is to explore the potential of UAVs for non-destructive yield prediction at various crop growth stages by integrating UAVs-based RS with machine learning, while also screening for drought-resistant and water-saving variety based on predicted yields, actual evapotranspiration (ET) derived from soil water balance and water use efficiency (WUE) at grain yield level. The results indicate that the random forest regression (RFR) model achieved the best prediction results. The optimal data combination of RS, canopy temperature, and data of variety by using RFR yielded the highest coefficient of determination (R2). Additionally, the RFR performs best when using data from the mid-filling stage (single-stage data) and the entire growth stage data (multi-stage data), with R2 0.58 and 0.69, respectively. Among the varieties, Malan 1 and Jimai 765 ranked first and second in both predicted and measured yield assessments, indicating the reliability of the yield prediction model for top-performing varieties. By combining predicted yields from RFR with ET, the screening results demonstrated high consistency between predicted and measured yields. Notably, even yield prediction models with lower R2 can still provide satisfactory screening results. These findings will contribute to screening drought-resistant and water-saving winter wheat varieties by UAV. This research accelerates the variety screening process and addresses the conflict between agricultural production and water scarcity in the North China Plain.