We present the results of a combined U-series isotope and numerical modeling study of the 1912 Katmai-Novarupta eruption in Alaska. A stratigraphically constrained set of samples have compositions that range from basalt through basaltic andesite, andesite, dacite, and rhyolite. The major and trace element range can be modeled by 80–90% closed-system crystal fractionation over a temperature interval from 1279°C to 719°C at 100 MPa, with an implied volume of parental basalt of ∼65 km³. Numerical models suggest, for wall rock temperatures appropriate to this depth, that 90% of this volume of magma would cool and crystallize over this temperature interval within a few tens of kiloyears. However, the range in ⁸⁷Sr/⁸⁶Sr, (²³⁰Th/²³⁸U), and (²²⁶Ra/²³⁰Th) requires open-system processes. Assimilation of the host sediments can replicate the range of Sr isotopes. The variation of (²²⁶Ra/²³⁰Th) ratios in the basalt to andesite compositional range requires that these were generated less than several thousand years before eruption. Residence times for dacites are close to 8000 years, whereas the rhyolites appear to be 50–200 kyr old. Thus, the magmas that erupted within only 60 h had a wide range of crustal residence times. Nevertheless, they were emplaced in the same thermal regime and evolved along similar liquid lines of descent from parental magmas with similar compositions. The system was built progressively with multiple inputs providing both mass and heat, some of which led to thawing of older silicic material that provided much of the rhyolite.