Protracted volcanic eruptions may exhibit unanticipated intensifications in explosive behaviour and attendant hazards. Santiaguito dome complex, Guatemala, has been characterised by century-long effusion interspersed with frequent, small-to-moderate (<2 km high plumes) gas-and-ash explosions. During 2015–2016, explosions intensified generating hazardous ash-rich plumes (up to 7 km high) and pyroclastic flows. Here, we integrate petrological, geochemical and geophysical evidence to evaluate the causes of explosion intensification. Seismic and infrasound signals reveal progressively longer repose intervals between explosions and deeper fragmentation levels as the seismic energy of these events increased by up to four orders of magnitude. Evidence from geothermobarometry, bulk geochemistry and groundmass microlite textures reveal that the onset of large explosions was concordant with a relatively fast ascent of a deeper-sourced (∼17–24 km), higher temperature (∼960–1020◦C) and relatively volatile-rich magma compared to the previous erupted lavas, which stalled at ∼2 km depth and mingled with the left-over mush that resided beneath the pre-2015 lava dome. ... mehrWe interpret that purging driven by the injection of this deep-sourced magma disrupted the long-term activity, driving a transition from low energy shallow shear-driven fragmentation, to high energy deeper overpressure-driven fragmentation that excavated significant portions of the conduit and intensified local volcanic hazards. Our findings demonstrate the value of multi-parametric approaches for understanding volcanic processes and the triggers for enigmatic shifts in eruption style, with the detection of vicissitudes in both monitoring signals and petrological signatures of the eruptive products proving paramount.