Hyperspectral reflectance sensing provides a rapid and cost-effective technique for assessing the suitability of groundwater for irrigation by monitoring real-time changes in its quality at a large scale. In this study, we assessed the quality of 15 groundwater samples from El Fayoum depression in the Western Desert (WD) and 25 groundwater samples from the Central Nile Delta (CND) in Egypt using a traditional approach of the physiochemical parameters, irrigation water quality indicators (IWQIs), and hydrochemical facies. The spectral reflectance data of the water surface was used to build new simple reflectance indices (SRIs), and the performance of these indices for assessing IWQIs was compared with those by partial least square regression (PLSR) that was based on all SRIs or the full-spectrum ranges. Generally, the groundwater of the CND was fresher and more suitable for irrigation purposes than those of the WD. Based on the six IWQIs, ~6.7–60.0% and 85.0–100.0% of the groundwater samples of the WD and CND, respectively, were categorized as highly suitable for irrigation purposes. Based on hydrochemical facies, Na-Cl and Ca-HCO3 were dominant in the WD and CND, respectively, as well as the alkali earth metals (Na+ + K+), which significantly exceeded the alkaline earth metals (Ca2+ + Mg2+) in the WD, with the reverse for the CND. Most developed SRIs had a moderate, weak, and moderate to strong relationship with physiochemical parameters and IWQIs in the WD, CND, and across both regions, respectively. The PLSR models based on all SRIs provided a more accurate estimation of IWQIs in calibration and validation datasets than those based on full-spectrum ranges, and both PLSR models provided better estimation than the individual SRIs. These findings support the feasibility of using ground reflectance measurements as a fast and low-cost tool for the assessment and management of groundwater for irrigation in arid and semiarid regions.