The degradation of groundwater (GW) quality due to seawater intrusion (SWI) is a major water security issue in water-scarce regions. This study aims to delineate the impact of SWI on the GW quality of a multilayered aquifer system in the eastern coastal region of Saudi Arabia. The physical and chemical properties of the GW were determined via field investigations and laboratory analyses. Irrigation indices (electrical conductivity (EC), potential salinity (PS), sodium adsorption ratio (SAR), Na%, Kelly’s ratio (KR), magnesium adsorption ratio (MAR), and permeability index (PI)) and a SWI index (fsea) were obtained to assess the suitability of GW for irrigation. K-mean clustering, correlation analysis, and principal component analysis (PCA) were used to determine the relationship between irrigation hazard indices and the degree of SWI. The tested GW samples were grouped into four clusters (C1, C2, C3, and C4), with average SWI degrees of 15%, 8%, 5%, and 2%, respectively. The results showed that the tested GW was unsuitable for irrigation due to salinity hazards. However, a noticeable increase in sodium and magnesium hazards was also observed. Moreover, increasing the degree of SWI (fsea) was associated with increasing salinity, sodium, and magnesium, with higher values observed in the GW samples in cluster C1, followed by clusters C2, C3, and C4. The correlation analysis and PCA results illustrated that the irrigation indices, including EC, PS, SAR, and MAR, were grouped with the SWI index (fsea), indicating the possibility of using them as primary irrigation indices to reflect the impact of SWI on GW quality in coastal regions. The results of this study will help guide decision-makers toward proper management practices for SWI mitigation and enhancing GW quality for irrigation.