Unmanned aerial vehicle (UAV)-based multispectral sensors have great potential in crop monitoring due to their high flexibility, high spatial resolution, and ease of operation. Image preprocessing, however, is a prerequisite to make full use of the acquired high-quality data in practical applications. Most crop monitoring studies have focused on specific procedures or applications, and there has been little attempt to examine the accuracy of the data preprocessing steps. This study focuses on the preprocessing process of a six-band multispectral camera (Mini-MCA6) mounted on UAVs. First, we have quantified and analyzed the components of sensor error, including noise, vignetting, and lens distortion. Next, different methods of spectral band registration and radiometric correction were evaluated. Then, an appropriate image preprocessing process was proposed. Finally, the applicability and potential for crop monitoring were assessed in terms of accuracy by measurement of the leaf area index (LAI) and the leaf biomass inversion under variable growth conditions during five critical growth stages of winter wheat. The results show that noise and vignetting could be effectively removed via use of correction coefficients in image processing. The widely used Brown model was suitable for lens distortion correction of a Mini-MCA6. Band registration based on ground control points (GCPs) (Root-Mean-Square Error, RMSE = 1.02 pixels) was superior to that using PixelWrench2 (PW2) software (RMSE = 1.82 pixels). For radiometric correction, the accuracy of the empirical linear correction (ELC) method was significantly higher than that of light intensity sensor correction (ILSC) method. The multispectral images that were processed using optimal correction methods were demonstrated to be reliable for estimating LAI and leaf biomass. This study provides a feasible and semi-automatic image preprocessing process for a UAV-based Mini-MCA6, which also serves as a reference for other array-type multispectral sensors. Moreover, the high-quality data generated in this study may stimulate increased interest in remote high-efficiency monitoring of crop growth status.