Plant potassium content (PKC) is a crucial indicator of crop potassium nutrient status and is vital in making informed fertilization decisions in the field. This study aims to enhance the accuracy of PKC estimation during key potato growth stages by using vegetation indices (VIs) and spatial structure features derived from UAV-based multispectral sensors. Specifically, the fraction of vegetation coverage (FVC), gray-level co-occurrence matrix texture, and multispectral VIs were extracted from multispectral images acquired at the potato tuber formation, tuber growth, and starch accumulation stages. Linear regression and stepwise multiple linear regression analyses were conducted to investigate how VIs, both individually and in combination with spatial structure features, affect potato PKC estimation. The findings lead to the following conclusions: (1) Estimating potato PKC using multispectral VIs is feasible but necessitates further enhancements in accuracy. (2) Augmenting VIs with either the FVC or texture features makes potato PKC estimation more accurate than when using single VIs. (3) Finally, integrating VIs with both the FVC and texture features improves the accuracy of potato PKC estimation, resulting in notable R 2 values of 0.63, 0.84, and 0.80 for the three fertility periods, respectively, with corresponding root mean square errors of 0.44%, 0.29%, and 0.25%. Overall, these results highlight the potential of integrating canopy spectral information and spatial-structure information obtained from multispectral sensors mounted on unmanned aerial vehicles for monitoring crop growth and assessing potassium nutrient status. These findings thus have significant implications for agricultural management.