Cotton (Gossypium hirsutum L.), as a significant economic crop, has undergone significant modernization in planting methods, and its smart irrigation management relies heavily on accurate cotton water content (CWC) estimation. Existing ground-based methods for measuring CWC are constrained by their limited scope and high monitoring costs. Although the development of unmanned aerial vehicle (UAV) technology has provided a new opportunity for large-scale CWC measurements, there remains a gap in the study of CWC estimation in cotton using multi-source and multi-stage data. In this study, we used UAV-based data, including texture features, vegetation indices, and a heat index, and applied four machine learning algorithms, i.e., partial least-squares regression (PLSR), support vector regression (SVR), random forest regression (RFR), and extreme gradient boosting (XGB), to estimate CWC. The findings demonstrate that in a single growth stage, the boll setting stage performs the best, and multi-source and multi-stage inputs can improve the accuracy of CWC estimation, with the best performance of XGB (R² = 0.860). Overall, this study highlights that the synergistic use of multi-source and multi-stage data can effectively improve CWC estimation in cotton, suggesting UAV-based data will lead to a brighter future for precision agriculture.