Grain yield is one of the most critical indicators for evaluating the performance of wheat breeding. However, the assessment process, from early-stage breeding lines to officially registered varieties that have passed the DUS (Distinctness, Uniformity, and Stability) test, is often time-consuming and labor-intensive. Multispectral remote sensing based on unmanned aerial vehicles (UAVs) has demonstrated significant potential in crop phenotyping and yield estimation due to its high throughput, non-destructive nature, and ability to rapidly collect large-scale, multi-temporal data. In this study, multi-temporal UAV-based multispectral imagery, RGB images, and canopy height data were collected throughout the entire wheat growth stage (2023–2024) in Xuzhou, Jiangsu Province, China, to characterize the dynamic growth patterns of both breeding lines and registered cultivars. Vegetation indices (VIs), texture parameters (Tes), and a time-series crop height model (CHM), including the logistic-derived growth rate (GR) and the projected area (PA), were extracted to construct a comprehensive multi-source feature set. Four machine learning algorithms, namely a random forest (RF), support vector machine regression (SVR), extreme gradient boosting (XGBoost), and partial least squares regression (PLSR), were employed to model and estimate yield. The results demonstrated that spectral, texture, and canopy height features derived from multi-temporal UAV data effectively captured phenotypic differences among wheat types and contributed to yield estimation. Features obtained from later growth stages generally led to higher estimation accuracy. The integration of vegetation indices and texture features outperformed models using single-feature types. Furthermore, the integration of time-series features and feature selection further improved predictive accuracy, with XGBoost incorporating VIs, Tes, GR, and PA yielding the best performance (R² = 0.714, RMSE = 0.516 t/ha, rRMSE = 5.96%). Overall, the proposed multi-source modeling framework offers a practical and efficient solution for yield estimation in early-stage wheat breeding and can support breeders and growers by enabling earlier, more accurate selection and management decisions in real-world production environments.