The Irish Midlands region contains one of the world’s largest hydrothermal Zn-Pb ore districts, but uncertainty exists in the timing of mineralization relative to host rock ages. Consequently, genetic models for ore formation are poorly constrained and remain controversial. Here we use Re-Os geochronology to show that ore-stage pyrite from the Lisheen deposit formed at 346.6 ± 3.0 Ma, shortly after host rock deposition. Pyrite from the Silvermines deposit returns an age of 334.0 ± 6.1 Ma, indicating that at least some mineralization occurred during later burial. These age determinations show that the much younger paleomagnetic ages reported for the Irish Zn-Pb deposits reflect remagnetization during the Variscan orogeny, a process that we suggest affects paleomagnetic dating more widely. The Re-Os ages overlap with the ages of lower Carboniferous volcanic rocks in the Midlands, which are the product of magmatism that has been invoked as the driving force for hydrothermal activity. The relatively low initial Os ratios for both Lisheen (0.253 ± 0.045) and Silvermines (0.453 ± 0.006) are compatible with derivation of Os from these magmas, or from the Caledonian basement that underlies the ore deposits.