Strong, strato-volcanic eruptions are a substantial, intermittent source of natural climate variability. Initial atmospheric and oceanic conditions, such as El Niño Southern Oscillation (ENSO) and the North Atlantic Oscillation (NAO), also naturally impact climate on interannual timescales. We examine how initial conditions of ENSO and NAO contribute to the evolution of climate in the period following a Pinatubo-type eruption using a large (81-member) ensemble of model simulations in GISS model E2.1-G. Simulations are initialized from sampled conditions of ENSO and NAO using the protocol of the coordinated CMIP6 Volcanic Model Intercomparison Project (VolMIP) – where aerosols are forced with respect to time, latitude, and height. We analyze paired anomalous variations (perturbed – control) to understand changes in global and regional climate responses under positive, negative, and neutral ENSO and NAO conditions. In particular, we find that for paired anomalies there is a high probability of strong (∼1.5 ∘C) warming of northern Eurasia surface air temperature in the first winter after the volcanic eruption for negative NAO ensembles coincident with decreased lower stratospheric temperature at the poles, decreased geopotential height, and strengthening of the stratospheric polar vortex. Climate anomalies (relative to average conditions across the control period), however, show no mean warming and suggest that the strength of this response is impacted by conditions present in the selected period of the control run. Again using paired anomalies, we also observe that under both +ENSO and −ENSO ensembles sea surface temperature decreases in the first post-eruptive boreal winter coinciding with surface cooling from volcanic aerosols. Neutral ENSO ensembles, on the other hand, show variability in their response with no clear trend in post-eruptive warming or cooling. In general, paired anomalies from unperturbed simulations give insight into the evolution of the climate response to volcanic forcing; however, when compared with anomalies from climatological conditions, it is clear that paired anomalies are significantly affected by sampled initial conditions occurring at the time of the volcanic eruption.