Timely monitoring and precise estimation of the leaf chlorophyll contents of maize are crucial for agricultural practices. The scale effects are very important as the calculated vegetation index (VI) were crucial for the quantitative remote sensing. In this study, the scale effects were investigated by analyzing the linear relationships between VI calculated from red-green-blue (RGB) images from unmanned aerial vehicles (UAV) and ground leaf chlorophyll contents of maize measured using SPAD-502. The scale impacts were assessed by applying different flight altitudes and the highest coefficient of determination (R) can reach 0.85. We found that the VI from images acquired from flight altitude of 50 m was better to estimate the leaf chlorophyll contents using the DJI UAV platform with this specific camera (5472 × 3648 pixels). Moreover, three machine-learning (ML) methods including backpropagation neural network (BP), support vector machine (SVM), and random forest (RF) were applied for the grid-based chlorophyll content estimation based on the common VI. The average values of the root mean square error (RMSE) of chlorophyll content estimations using ML methods were 3.85, 3.11, and 2.90 for BP, SVM, and RF, respectively. Similarly, the mean absolute error (MAE) were 2.947, 2.460, and 2.389, for BP, SVM, and RF, respectively. Thus, the ML methods had relative high precision in chlorophyll content estimations using VI; in particular, the RF performed better than BP and SVM. Our findings suggest that the integrated ML methods with RGB images of this camera acquired at a flight altitude of 50 m (spatial resolution 0.018 m) can be perfectly applied for estimations of leaf chlorophyll content in agriculture.