The objective of our study is to estimate the contamination concentrations in the Permian Basin, US. A total of 481 observation samples were chosen within the following study areas: Andrews, Martin, Midland, Ector, Crane, and Upton Counties. The Dockum, Pecos Valley, Edwards-Trinity Plateau, and Ogallala aquifers were evaluated for inorganic contaminants. Level reports for parameters such as Arsenic (As), Nitrate (NO3−), Fluoride (F), Chloride (Cl), total dissolved solids (TDS), and Uranium (U) were provided by the Texas Water Development Board (TWDB) analyzed with other counties. We demonstrated the average level in each county with different time periods: 1992–2005 and 2006–2019. Our results were compared with the Environmental Protection Agency (EPA) standards and concluded the safety of water consumption in the study areas. We concluded that inorganic pollutants resulted mainly from human impacts such as agriculture, fertilizers, and energy developments. This research offers significant information about inorganic pollutants and brackish aquifers in the Permian Basin, US, contributing to our understanding of how groundwater resources respond to contaminations in dry regions. With freshwater becoming scarcer in arid climates such as the Permian Basin, US, it is important to ensure successful water management in these dry and arid locations.