The flow regimes of glacier-fed rivers are sensitive to climate change due to strong climate–cryosphere–hydrosphere interactions. Previous modelling studies have projected changes in annual and seasonal flow magnitude but neglect other changes in river flow regime that also have socio-economic and environmental impacts. This study employs a signature-based analysis of climate change impacts on the river flow regime for the deglaciating Virkisá river basin in southern Iceland. Twenty-five metrics (signatures) are derived from 21st century projections of river flow time series to evaluate changes in different characteristics (magnitude, timing and variability) of river flow regime over sub-daily to decadal timescales. The projections are produced by a model chain that links numerical models of climate and glacio-hydrology. Five components of the model chain are perturbed to represent their uncertainty including the emission scenario, numerical climate model, downscaling procedure, snow/ice melt model and runoff-routing model. The results show that the magnitude, timing and variability of glacier-fed river flows over a range of timescales will change in response to climate change. For most signatures there is high confidence in the direction of change, but the magnitude is uncertain. A decomposition of the projection uncertainties using analysis of variance (ANOVA) shows that all five perturbed model chain components contribute to projection uncertainty, but their relative contributions vary across the signatures of river flow. For example, the numerical climate model is the dominant source of uncertainty for projections of high-magnitude, quick-release flows, while the runoff-routing model is most important for signatures related to low-magnitude, slow-release flows. The emission scenario dominates mean monthly flow projection uncertainty, but during the transition from the cold to melt season (April and May) the snow/ice melt model contributes up to 23 % of projection uncertainty. Signature-based decompositions of projection uncertainty can be used to better design impact studies to provide more robust projections.