Active subaerial geothermal systems are regarded as modern analogues of low- to intermediate-sulfidation epithermal Au–Ag deposits, where minor amounts of Cu are mostly present as chalcopyrite. Although trace element data concerning sulfides are scarce in active geothermal systems at convergent settings, studies in several other environments have demonstrated that chalcopyrite is a relevant host of Ag and other trace elements. Here, we focus on the active Cerro Pabellón geothermal system in the Altiplano of northern Chile, where chalcopyrite-bearing samples were retrieved from a 561 m drill core that crosscuts the high-enthalpy geothermal reservoir at depth. A combination of EMPA and LA-ICP-MS data shows that chalcopyrite from Cerro Pabellón is silver-rich (Ag > 1000 ppm) and hosts a wide range of trace elements, most notably Se, Te, Zn, Sb, As, and Ni, which can reach 100 s of ppm. Other elements detected include Co, Pb, Cr, Ga, Ge, Sn, Cd, and Hg but are often present in low concentrations (<100 ppm), whereas Au, Bi, Tl, and In are generally below 1 ppm. Chalcopyrite shows a distinct geochemical signature with depth, with significantly higher Ag concentrations in the shallow sample (494 m) and increasing Cd and In contents towards the bottom of the studied drill core (549 m). These differences in the trace element contents of chalcopyrite are interpreted as related to temperature gradients during the waning stages of boiling at Cerro Pabellón, although further studies are still needed to assess the precise partitioning controls. Our data provide evidence that chalcopyrite may play a relevant role as a scavenger of certain metals and a monitor of fluid changes in hydrothermal systems.