Long-term eruptive activity at the Santiaguito lava dome complex, Guatemala, is characterised by the regular occurrence of small-to-moderate size explosions from the active Caliente dome. Between November 2014 and December 2018, we deployed a seismo-acoustic network at the volcano, which recorded several changes in the style of eruption, including a period of elevated explosive activity in 2016. Here, we use a new catalogue of explosions to characterise changes in the eruptive regime during the study period. We identify four different phases of activity based on changes in the frequency and magnitude of explosions. At the two ends of the spectrum of repose times we find pairs of explosions with near-identical seismic and acoustic waveforms, recorded within 1–10 min of one another, and larger explosions with recurrence times on the order of days to weeks. The magnitude-frequency relationship for explosions at Santiaguito is well described by a power-law; we show that changes in b-value between eruptive regimes reflect temporal and spatial changes in rupture mechanisms, likely controlled by variable magma properties. We also demonstrate that the distribution of inter-explosion repose times between and within phases is well represented by a Poissonian process. The Poissonian distribution describing repose times changes between and within phases as the source dynamics evolve. We find that changes in source properties restrict the extrapolation of explosive behaviour to within a given eruptive phase, limiting the potential for long-term assessments of anticipated eruptive behaviour at Santiaguito.