The Southern Hemisphere Antarctic stratosphere experienced two noteworthy events in 2015: a significant injection of sulfur from the Calbuco volcanic eruption in Chile in April, and a record-large Antarctic ozone hole in October and November. Here, we quantify Calbuco's influence on stratospheric ozone depletion in austral spring 2015 using observations and an earth system model. We analyze ozonesondes, as well as data from the Microwave Limb Sounder. We employ the Community Earth System Model, version 1, with the Whole Atmosphere Community Climate Model (CESM1(WACCM)) in a specified dynamics setup, which includes calculations of volcanic effects. The Cloud Aerosol Lidar with Orthogonal Polarization data indicate enhanced volcanic liquid sulfate 532 nm backscatter values as far poleward as 68°S during October and November (in broad agreement with WACCM). Comparison of the location of the enhanced aerosols to ozone data supports the view that aerosols played a major role in increasing the ozone hole size, especially at pressure levels between 150 and 100 hPa. Ozonesonde vertical ozone profiles from the sites of Syowa, South Pole, and Neumayer, display the lowest individual October or November measurements at 150 hPa since the 1991 Mt. Pinatubo eruption period, with Davis showing similarly low values, but no available 1990s data. The analysis suggests that under the cold conditions ideal for ozone depletion, stratospheric volcanic aerosol particles from the moderate-magnitude eruption of Calbuco in 2015 greatly enhanced austral ozone depletion, particularly at 55–68°S, where liquid binary sulfate aerosols have a large influence on ozone concentrations.