Volcán Mocho-Choshuenco (39°55’S 72°2’W) is one of the most hazardous volcanoes in Chile’s Southern Volcanic Zone (SVZ). To better evaluate these hazards, we have reconstructed a high resolution eruption history, the most detailed to date for a volcano in Chile, from detailed field observations and geochemical analyses. Mocho-Choshuenco has experienced ca. 75 post-glacial (< 18 ka) explosive eruptions, including three large (volume ≥ 1 km3) Plinian eruptions (Neltume, Pirehueico and Huilo) and a large pyroclastic density current and associated sub-Plinian event (Enco). Poor preservation and lack of exposure made it difficult to distinguish between medial to distal deposits solely on field observations. Instead, deposits have been correlated using a combination of glass chemistry and Fe-Ti oxide compositions. New radiocarbon dates were obtained and integrated with existing dates in a Bayesian age model (OxCal) to constrain the tempo of the volcanism. Based on preserved deposits, we derive a post-glacial eruptive frequency of one explosive eruption every ~ 220 years with the youngest, confirmed eruption from Mocho-Choshuenco in 1864. The total post-glacial volume of tephra erupted is estimated at ≥ 20 km3 (ca. 50% with a dacitic or rhyolitic glass composition) with ≥ 4 km3 erupted from the monogenetic cones on the flanks, making Mocho-Choshuenco one of the most productive (ca. 1 km3/kyr) and active volcanoes in the SVZ during post-glacial times. Many tephra deposits from Mocho-Choshuenco could be preserved in one or more lakes in the region, and have the potential to form regional tephra markers. In particular the Neltume deposits, which are dispersed to the NNE, are found interbedded with tephra deposits from the Villarrica – Quetrupillán – Lanín chain and should be preserved around Sollipulli and Llaima (~ 140 km NNE of Mocho-Choshuenco). This study highlights how a multi-technique approach enables a complicated tephrostratigraphy to be unravelled so more robust estimates of the past eruptive frequency and size can be determined.