The Middle Cambrian Mount Read Volcanics of western Tasmania, Australia, host several world-class volcanic-hosted massive sulfide (VHMS) deposits, representing a wide range of deposit styles. Although the deposits and their host sequences are variably deformed and locally preserve spectacular examples of primary textures and structures, rapid lateral and vertical facies changes, and faults with uncertain sense and magnitude of displacement, have made it impossible to correlate stratigraphy across the belt. Previous dating studies in the area have yielded relatively imprecise crystallization ages. We have employed the chemical abrasion isotope dilution thermal ionization mass spectroscopy (ID-TIMS) U-Pb zircon method to obtain highly precise crystallization ages for a total of 18 samples of volcanic and intrusive rock units from throughout the Mount Read Volcanics and underlying mafic-ultramafic complexes. The new data permit detailed resolution of age relationships within the belt. The study establishes an age of 516.0 ± 0.9 Ma for the McIvor Hill gabbro, which is part of a mafic-ultramafic complex interpreted to underlie the Mount Read Volcanics. Magmatism in the central Mount Read Volcanics lasted at least 12.7 m.y., from 506.8 ± 1.0 Ma for a massive dacite unit in the lower part of the Central Volcanic Complex to 496.0 ± 0.9 Ma for a welded ignimbrite in the lower Tyndall Group. Together with previous age constraints, results of the study provide a precise chronostratigraphic framework for magmatism and VHMS deposit formation within the Mount Read Volcanics. The precise age data indicate that, north of the Henty fault, magmatism occurred in three discrete pulses, at least two of which were separated by periods of sedimentation. We demonstrate that VHMS deposits in the Mount Lyell, Roseberry-Hercules, and Que-Hellyer districts, comprising the majority of the known, significant VHMS deposits in the belt, formed within a narrow time interval at ~500 ± 1 Ma, at a relatively late stage in the evolution of the belt. Some of the larger intrusions in the belt (e.g., the Bonds Range porphyry; 500.4 ± 0.8 Ma) were emplaced contemporaneously with VHMS deposit formation; however, other bodies such as the Murchison granite (497.3 ± 0.9 Ma) are younger than the deposits and are unlikely to have been involved in their genesis as has previously been suggested. These conclusions will aid explorers in targeting VHMS mineralization in the Mount Read Volcanics.