Single-atom catalysts1 make exceptionally efficient use of expensive noble metals and can bring out unique properties1–3. However, applications are usually compromised by limited catalyst stability, which is due to sintering3,4. Although sintering can be suppressed by anchoring the metal atoms to oxide supports1,5,6, strong metal–oxygen interactions often leave too few metal sites available for reactant binding and catalysis6,7, and when exposed to reducing conditions at sufficiently high temperatures, even oxide-anchored single-atom catalysts eventually sinter4,8,9. Here we show that the beneficial effects of anchoring can be enhanced by confining the atomically dispersed metal atoms on oxide nanoclusters or ‘nanoglues’, which themselves are dispersed and immobilized on a robust, high-surface-area support. We demonstrate the strategy by grafting isolated and defective CeOx nanoglue islands onto high-surface-area SiO2; the nanoglue islands then each host on average one Pt atom. We find that the Pt atoms remain dispersed under both oxidizing and reducing environments at high temperatures, and that the activated catalyst exhibits markedly increased activity for CO oxidation. We attribute the improved stability under reducing conditions to the support structure and the much stronger affinity of Pt atoms for CeOx than for SiO2, which ensures the Pt atoms can move but remain confined to their respective nanoglue islands. The strategy of using functional nanoglues to confine atomically dispersed metals and simultaneously enhance their reactivity is general, and we anticipate that it will take single-atom catalysts a step closer to practical applications. Nanometre-sized ‘nanoglue’ islands of CeOx on high-surface-area SiO2 are shown to suppress sintering and confine on average one Pt atom per island, leading to stable single-atom catalysts under oxidizing and reducing environments.