Distinguishing periods of intermittent unrest from the run-up to eruption is a major challenge at volcanoes around the globe. Comparing multidisciplinary monitoring data with mineral chemistry that records the physical and spatio-temporal evolution of magmas fundamentally advances our ability to forecast eruptions. The recent eruption of Mauna Loa, Earth’s largest active volcano, provides a unique opportunity to differentiate unrest from run-up and improve forecasting of future eruptions. After decades of intermittent seismic and geodetic activity over 38 years of repose, Mauna Loa began erupting on 27 November 2022. Here we present a multidisciplinary synthesis that tracks the spatio-temporal evolution of precursory activity by integrating mineral and melt chemistry, fluid inclusion barometry, numerical modeling of mineral zoning, syn-eruptive gas plume measurements, the distribution and frequency of earthquake hypocenters, seismic velocity changes, and ground deformation. These diverse data indicate that the eruption occurred following a 2-month period of sustained magma intrusion from depths of 3–5 km up to 1–2 km beneath the summit caldera, providing a new model of the plumbing system at this very high threat volcano. Careful correlation of both the geochemistry and instrumental monitoring data improves our ability to distinguish unrest from the run-up to eruption by providing deeper understanding of the both the monitoring data and the magmatic system—an approach that could be applied at other volcanic systems worldwide.