Hydrothermal units are characterized by the emergence of several large-flow thermo-mineral springs (griffons), each with varying temperature and physico-chemical characteristics depending on the point of emergence. It seems, however, that there is variability between the different systems, although it is not easy to characterize it because the variability within each system is high. The regional dimension of the chemical composition of thermal waters is, therefore, an aspect that has received very little attention in the literature due to the lack of access to the deep reservoir. In this study, we investigated the spatial variability, on a regional scale, in the characteristics of thermal waters in northeastern Algeria, and more specifically the hydrothermal systems of Guelma, Souk Ahras, Khenchela and Tébessa. Thirty-two hot water samples were taken between December 2018 and October 2019, including five samples of low-temperature mineral spring water. Standard physico-chemical parameters, major anions and cations and lithium were analyzed. The data were log-transformed data and processed via principal component analysis, discriminant analysis and unsupervised classification. The results show that thermal waters are the result of a mixture of hot waters, whose chemical profile has a certain local character, and contaminated by cold surface waters. These surface waters may also have several chemical profiles depending on the location. In addition to the internal variability in each resource, there are differences in water quality between these different hydrothermal systems. The Guelma region differs the most from the other thermal regions studied, with a specific calcic sulfate chemical profile. This question is essential for the rational development of these regional resources in any field whatsoever.