A multi-mineral oxygen isotope study sheds light on the origin, cooling and alteration of Late Neoproterozoic A-type granites in the Arabian–Nubian shield of southern Israel. The oxygen isotope ratio of zircon of the Timna monzodiorite, quartz syenite and alkaline granite are within the range of mantle zircon (δ18O(Zrn) = 5.3 ± 0.6‰, 2σ), supporting the co-genetic mantle-derived origin previously suggested based on geochemical data and similar ɛNd(T) values and U–Pb ages (610 Ma). Likewise, olivine norite xenoliths within the monzodiorite (δ18O(Ol) = 5.41 ± 0.07‰) may have formed as cumulate in a parent mantle-derived magma. Within the Timna igneous complex, the latest and most evolved intrusion, an alkaline granite, has the least contaminated isotope ratio (δ18O(Zrn) = 5.50 ± 0.02‰), whereas its inferred parental monzodiorite magma has slightly higher and more variable δ18O(Zrn) values (5.60 to 5.93‰). The small isotope variation may be accounted for either by small differences in the temperature of zircon crystallization or by minor contamination of the parent magma followed by shallow emplacement and intrusion by the Timna alkaline granite. The Timna alkaline granite evolved, however, from a non-contaminated batch of mantle-derived magma. The formation of Yehoshafat granite (605 Ma; δ18O(Zrn) = 6.63 ± 0.10‰), exposed ~30 km to the south of the mineralogically comparable Timna alkaline granite, involved significant contribution from supracrustal rocks. A-type granites in southern Israel thus formed by differentiation of mantle-derived magma and upper crustal melting coevally. Fast grain boundary diffusion modelling and measured quartz-zircon fractionations demonstrate that the Timna and Yehoshafat alkaline granites cooled very rapidly below 600 °C in accordance with being epizonal. One to three orders of magnitude slower cooling is calculated for 30 Ma older calc-alkaline granites of the host batholith, indicating a transition from thick orogenic to extended crust. Significant elevation of the δ18O of feldspars occurred through water–rock interaction at moderate temperatures (100–250 °C), most probably during a thermal event in Early Carboniferous times.