Leaf area index (LAI) serves as a pivotal parameter in crop monitoring, significantly impacting agricultural applications. Empirical models are one of the commonly used methods for estimating LAI, they are often dependent on vegetation indices (VIs), predominantly derived from low-to-moderate spatial resolution satellite sensors. A critical limitation of these VIs is their tendency to saturate at elevated LAI values. Additionally, the interplay between chlorophyll content (Cab), LAI, as well as average leaf inclination angle (ALA), particularly in reflectance spectra from red to red-edge regions, has been underexplored in past research. Based on Sentinel-2 satellite, with three red-edge bands and enhanced spatio-temporal resolution, this study introduced a new three red-edge vegetation index (VI3RE), comprising NDVI3RE and CI3RE, which leverages the unique spectral characteristics of these bands and related differential response to LAI and Cab variations. We investigated VI3RE’s efficacy through a threefold approach: firstly, by conducting sensitivity analyses using noise equivalent (NE)ΔLAI ((NE) ΔLAI=1.37 and 1.59 for NDVI3RE and CI3RE; (NE)ΔLAI = 1.75 – 3.25 for other VIs) and extended Fourier amplitude sensitivity test (EFAST) (the contribution of LAI: FOI > 30 % and TOI > 40 % for VI3RE; FOI ∼ 17 % − 28 % and TOI ∼ 25 % − 34 % for other VIs, except for NDVI with TOI ∼ 50 %), we demonstrated VI3RE’s heightened sensitivity to LAI and its improved capability for seasonal LAI estimation compared to other VIs. Secondly, by comprehensively considering the simplicity, interpretability, AIC and R2 values of various models, the linear regression model was selected for analyzing the relationships between LAI and various VIs. We established that VI3RE, particularly NDVI3RE, exhibits a robust correlation with LAI, thereby enhancing LAI estimation accuracy (R2 = 0.72, RMSE = 1.39). Lastly, we applied the LAI-VI regression models to generate crop LAI imageries throughout the growing season, subsequently validating by field measured LAI data. The results affirmed VI3RE’s superior performance in seasonal LAI estimation of crops, notably during peak growth and sowing phases. We conclude that the newly formulated VI3RE offers a universal, highly precise, and reliable model for LAI prediction across various crop types and phenological stages. However, the broader application of VI3RE may be limited, due to the three red-edge bands are not commonly found in most satellite platforms. In addition, some other aspects are not considered in this study, such as phenological information, meteorological factors, sampling strategies, etc., which should be meticulously considered in the future studies.