We present in situ laser ablation–multicollector–inductively coupled plasma–mass spectrometry Sr isotope data for plagioclase from a reference stratigraphic profile of the entire Layered Series and Upper Border Series of the Skaergaard intrusion (East Greenland). Plagioclase Sr isotope compositions and anorthite contents vary systematically from the margins of the intrusion inwards. The lowest 87Sr/86Sri (calculated at 56 Ma) values (∼0.7041) occur near the base and top of the intrusion and systematically increase over several lithostratigraphic zones to a value of ∼0.7044, which is uniform throughout the middle ∼2000 m of intrusion. Across this same profile, anorthite content of plagioclase varies smoothly from An65–70 at the base and top to ∼An25 approaching the purported “Sandwich Horizon.” Plagioclase near the roof and proximal to rafts of partially assimilated basement gneiss are markedly more radiogenic (87Sr/86Sri up to ∼0.7046). We explain the stratigraphic relationships by progressive contamination of the magma during early stages of differentiation by basement gneiss rafts entrained during emplacement and accumulated near the top of the chamber. Contamination was transient, ceasing once the entrained gneiss was consumed or isolated from the main magma reservoir as the solidification front advanced. Modeling of fractionation-assimilation processes accounts for the observed isotopic trends with only a few percent assimilation (relative to the original magma mass). The record of contamination revealed by Sr in plagioclase supports the view that the bulk of the Skaergaard intrusion formed by closed-system differentiation with only minor in situ contamination and no magma recharge. Comparing plagioclase and bulk-rock Sr suggests that the latter may have witnessed late-stage metasomatic overprinting of phases other than plagioclase.