Water samples (< 0.45 μm) from the Mejerda hydrographic system were analysed for trace metals and Pb isotopes, together with Pb isotope measurements of galena from the mines of the system. Water was collected (i) within the mines, (ii) in tributaries lying as close as possible to the mines, (iii) along the tributaries, (iv) along the main Mejerda River, and (v) in dammed lakes. All metal concentrations measured in the waters are below the limits given for health purposes of surface water, though some of them are close. Metals such as Al, V, Ni, Cu, Pb, and U are slightly enriched in the uppermost part of the system but they do not exceed 20 ppb (μg l−1), with the exception of Al reaching 120 ppb. In the lower Mejerda sector, a few high Zn concentrations of up to 550 ppb are observed, and up to 80 ppb for Ba. Lead isotopic compositions of 41 water samples show large variations, yielding ratios at 17.736–18.884 for 206Pb/204Pb, 15.504–15.977 for 207Pb/204Pb, and 37.135–39.992 for 208Pb/204Pb. In contrast, Pb isotopic compositions of 11 galena samples from different mines define a surprisingly narrow field, being systematically more radiogenic in 206Pb than water. Compared to water and galena, Pb in Tunisian gasoline has a very different and much less radiogenic Pb isotopic composition at 16.351, 15.493, and 36.135, respectively. No significant contribution of such gasoline Pb can be detected either in the main Mejerda River or the numerous tributaries. The same observation is made for galena Pb, with the particularity that water lying closest to the isotopic compositions of galena was sampled in the lower part of the system where mines are absent. For the upper part of the system, minor contributions from the mines cannot be ruled out. The full set of Pb isotopic data substantiates the ultimate sources of Pb to have evolved with large variations in time-integrated U/Th/Pb ratios, including differences in mantle extraction ages. Simple mixing between two end-members can be ruled out for most of the water Pb data. It is therefore suggested that Pb and other metals of Mejerda water originate from local soils, from where they can be leached from alteration phases. In contrast to water showing a wide variation of ultimate source lithologies, the particularly narrow field of galena Pb isotopic compositions requires Pb extraction from a surprisingly homogenous and strongly U- and Th-depleted reservoir. This reservoir is most likely the Triassic evaporites, essentially gypsum, forming in a well mixed water volume devoid of significant detrital input.