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Mineral dust is transported in the atmosphere and deposited in oceans, ice sheets and the terrestrial biosphere. Temporal changes in locations of dust source areas and transport pathways have implications for global climate and biogeochemical cycles. The chemical and physical characterization of the dust record preserved in ice cores is useful for identifying of dust source regions, dust transport, dominant wind direction and storm trajectories. Here, we present a 50,000-year geochemical characterization of mineral dust entrapped in a horizontal ice core from the Taylor Glacier in East Antarctica. Strontium (Sr) and neodymium (Nd) isotopes, grain size distribution, trace and rare earth element (REE) concentrations, and inorganic ion (Cl− and Na+) concentrations were measured in 38 samples, corresponding to a time interval from 46 kyr before present (BP) to present. The Sr and Nd isotope compositions of insoluble dust in the Taylor Glacier ice shows distinct changes between the Last Glacial Period (LGP in this study ranging from ∼46.7–15.3 kyr BP) the early Holocene (in this study ranging from ∼14.5–8.7 kyr BP), and zero-age samples. The 87Sr/86Sr isotopic composition of dust in the Taylor Glacier ice ranged from 0.708 to 0.711 during the LGP, while the variability during the early Holocene is higher ranging from 0.707 to 0.714. The eNd composition ranges from 0.1 to −3.9 during the LGP, and is more variable from 1.9 to −8.2 during the early Holocene. The increased isotopic variability during the early Holocene suggests a shift in dust provenance coinciding with the major climate transition from the LGP to the Holocene. The isotopic composition and multiple physical and chemical constraints support previous work attributing Southern South America (SSA) as the main dust source to East Antarctica during the LGP, and a combination of both local Ross Sea Sector dust sources and SSA after the transition into the Holocene. This study provides the first high time resolution data showing variations in dust provenance to East Antarctic ice during a major climate regime shift, and we provide evidence of changes in the atmospheric transport pathways of dust following the last deglaciation.