• LCC was estimated based on the UAV-based image analysis. • The response stability of vegetation index and LCC was analyzed under different coverage. • Different variable screening methods were used to optimize the spectral parameters. • The spatial distribution map of maize LCC was constructed to provide potentials for fertilization application. Efficiently estimating chlorophyll content is important in monitoring the photosynthesis capacity and growth status of maize canopy in precision agriculture management. Vegetation index (VI) easily obtained by proximal remote sensing has been used as a non-destructive and high-throughput way in crop monitoring, especially in chlorophyll estimation. However, the estimated results of the field chlorophyll content by VIs always face challenges from soil background inhibition and estimation stability under the dynamic changes of vegetation biomass. Thus, an unmanned aerial vehicle (UAV)-based chlorophyll content estimation was conducted by evaluating VI responses under different crop coverages. An analysis was conducted on 36 VIs under different crop coverage conditions to explore their response differences and robustness for chlorophyll estimation. This work focused on the three kinds of VIs named simple vegetation index, modified vegetation index, and functional vegetation index. In 2020, at the experimental station of Dryland Farming Institute of Hebei Academy of Agriculture and Forestry Sciences, UAV carrying multispectral sensor was used to collect visible and near-infrared images of the canopy at the jointing stage of maize under six fertilization levels to obtain VIs. After the UAV fled, ground calibration and sample collection were performed simultaneously, and chlorophyll content was measured. For data processing, correlation coefficient method (CCM) and maximal information coefficient (MIC) were first used to analyze the correlation response characteristics of VIs and chlorophyll content under three different coverage levels. The results showed that when the level of canopy coverage was increased, the linear correlation between VIs and chlorophyll content was substantially reduced. The MIC response indicating linear and non-linear combination relationship was more robust. In addition, the VIs obtained by UAV had a significant linear correlation with maize canopy chlorophyll under low (0.05–0.35) and medium (0.35–0.48) coverage, but an obvious non-linear correlation under high (0.48–0.75) coverage. Chlorophyll-sensitive parameters were then screened based on methods of CCM, MIC, and random frog method (RFM), respectively. Partial least squares regression (PLS) and random forest (RF) algorithms were used to establish the maize canopy chlorophyll content detection models. The findings showed that when Green minus red vegetation index (GMR), Red light normalized value (NRI), Normalized difference red edge (NDRE), Modified simple ratio with red edge (MSRREG), Enhanced Vegetation Index (EVI), Normalized red green difference vegetation index (NDIg), Normalized red blue difference vegetation index (NDIb), Soil-adjusted vegetation index (SAVI), Optimized soil-adjusted vegetation index with red edge (OSAVIREG), Soil-atmospherically resistant vegetation index (SARVI) were selected based on RFM as the optimal spectral variables, the chlorophyll content detection model constructed based on PLS had the least numbers of characteristic variables and the best model accuracy. The training set R 2 and RMSE were 0.753 and 2.089 mg/L, respectively, and the verification set R 2 and RMSE were 0.682 and 2.361 mg/L, respectively. Field chlorophyll content and detection error distribution maps were also drawn and combined with the distribution of fertilization management to provide support for the UAV monitoring of crop growth in the field and variable fertilization management decisions.