The coupling of remote sensing technology and crop growth models represents a promising approach to support crop yield prediction and irrigation management. In this study, five vegetation indices were derived from the Copernicus-Sentinel 2 satellite to investigate their performance monitoring winter wheat growth in a Mediterranean environment in Lebanon’s Bekaa Valley. Among those indices, the fraction of canopy cover was integrated into the AquaCrop model to simulate biomass and yield of wheat grown under rainfed conditions and fully irrigated regimes. The experiment was conducted during three consecutive growing seasons (from 2017 to 2019), characterized by different precipitation patterns. The AquaCrop model was calibrated and validated for different water regimes, and its performance was tested when coupled with remote sensing canopy cover. The results showed a good fit between measured canopy cover and Leaf Area Index (LAI) data and those derived from Sentinel 2 images. The R² coefficient was 0.79 for canopy cover and 0.77 for LAI. Moreover, the regressions were fitted to relate biomass with Sentinel 2 vegetation indices. In descending order of R², the indices were ranked: Fractional Vegetation Cover (FVC), LAI, the fraction of Absorbed Photosynthetically Active Radiation (fAPAR), the Normalized Difference Vegetation Index (NDVI), and the Enhanced Vegetation Index (EVI). Notably, FVC and LAI were highly correlated with biomass. The results of the AquaCrop calibration showed that the modeling efficiency values, NSE, were 0.99 for well-watered treatments and 0.95 for rainfed conditions, confirming the goodness of fit between measured and simulated values. The validation results confirmed that the simulated yield varied from 2.59 to 5.36 t ha⁻¹, while the measured yield varied from 3.08 to 5.63 t ha⁻¹ for full irrigation and rainfed treatments. After integrating the canopy cover into AquaCrop, the % of deviation of simulated and measured variables was reduced. The Root Mean Square Error (RMSE) for yield ranged between 0.08 and 0.69 t ha⁻¹ before coupling and between 0.04 and 0.42 t ha⁻¹ after integration. This result confirmed that the presented integration framework represents a promising method to improve the prediction of wheat crop growth in Mediterranean areas. Further studies are needed before being applied on a larger scale.