Standard methods are limited for monitoring and managing water quality indicators (WQIs) in real-time and on a large scale. Consequently, there is an urgent need to use reliable, practical, swift, and cost-effective monitoring tools that can be easily deployed and assist decision makers in assessing key indicators relevant to surface water quality in a comprehensive manner. Surface water samples were collected and evaluated for water quality at 16 distinct sites across the Qaroun Lake in 2018 and 2019. Different WQIs, including total dissolved solids (TDS), transparency, total suspended solids (TSS), chlorophyll-a (Chl-a), and total phosphorus (TP), were tested for aquatic utilization. An integrated approach comprising WQIs, geospatial techniques, hyperspectral reflectance indices (SRIs) (commonly used SRIs, two-band and three-band SRIs (Spectral index calculated from water spectral reflectance of two or three wavelengths)), and partial least square regression (PLSR) models were used to assess the water quality of Qaroun Lake. According to the findings, the water quality attributes are polluted to varying degrees. The majority of commonly used SRIs presented moderately relationship with four WQIs (transparency, TSS, Chl-a, and TP) (R2 = 0.45 to 0.64), while the majority of newly two-band SRIs (NSRIs-2b) indicated moderate to strong relationships with WQIs (R2 = 0.51 to 0.74), and the majority of newly three band SRIs (NSRIs-3b) presented strong relationships with WQIs (R2 = 0.67 to 0.81). Broadly, the highest coefficients of determination were noticed with the NSRIs-3b followed by the NSRIs-2b and then the commonly used SRIs. For example, the NSRIs-3b (NDSI648,712,696) had stronger relationships with transparency, TSS, and Chl-a with R2 = 0.77, 0.66, and 0.81, respectively, than other SRIs. In addition, the NSRIs-3b (NDSI620,610,622) showed the highest R2 of 0.73 with TSS. The NSRIs-3b coupling with PLSR predicted the WQIs with satisfactory accuracy in the calibration (reach up R2 = 0.85) and validation (reach up R2 = 0.81) datasets. The overall findings of this research study showed that deriving an optimized NSRIs-3b from spectrum region and combining it with PLSR model could be a practical tool for managing water quality of the Qaroun Lake by accurately, timely, and non-destructively monitoring the WQIs.