The Palaeogene Kangerlussuaq Intrusion (∼50 Ma) of East Greenland displays concentric zonation from quartz-rich nordmarkite (quartz syenite) at the margin, through pulaskite, to foyaite (nepheline syenite) in the centre; modal layering and igneous lamination are locally developed but there are no internal intrusive contacts. This is an apparent violation of the phase relations in Petrogeny's Residua System. We propose that this intrusion is layered, grading from quartz syenite at the bottom to nepheline syenite at the top. Mineral and whole-rock major and trace element data and Sr–Nd–Hf–Pb isotope data are presented that provide constraints on the petrogenesis of the intrusion. Radiogenic isotope data indicate a continuously decreasing crustal component from the quartz nordmarkites (87Sr/86Sr=0·7061; εNdi=2·3; εHfi=5·2; 206Pb/204Pbmeas=16·98) to the foyaites (87Sr/86Sr=0·7043–0·7044; εNdi=3·8–4·9; εHfi=10·7–11·1; 206Pb/204Pbmeas=17·78–17·88); the foyaites are dominated by a mantle isotopic signature. The average Mg-number of amphibole cores becomes increasingly primitive, varying from 26·4 in the nordmarkites to 57·4 in the pulaskites. Modal layering, feldspar lamination and the presence of huge basaltic xenoliths derived from the chamber roof, now resting on the transient chamber floor, demonstrate bottom-upwards crystallization. The intrusion cannot, therefore, have formed in a system closed to magmatic recharge. The lack of gneissic xenoliths in the nordmarkites suggests that most contamination took place deeper in the crust. In the proposed model, the nordmarkitic magma formed during crustal assimilation in the roof zone of a large, silica-undersaturated alkali basaltic/basanitic, stratified magma chamber, prior to emplacement in the uppermost crust. The more primitive syenites, terminating with foyaite at the top of the intrusion, formed as a consequence of repeated recharge of the Kangerlussuaq Intrusion magma chamber by tapping less contaminated, more primitive phonolitic melt from deeper parts of the underlying chamber during progressive armouring of the plumbing system.