Most of the world's hydrogen supply is currently obtained by reforming hydrocarbons. 'Reformate' hydrogen contains significant quantities of CO that poison current hydrogen fuel-cell devices. Catalysts are needed to remove CO from hydrogen through selective oxidation. Here, we report first-principles-guided synthesis of a nanoparticle catalyst comprising a Ru core covered with an approximately 1-2-monolayer-thick shell of Pt atoms. The distinct catalytic properties of these well-characterized core-shell nanoparticles were demonstrated for preferential CO oxidation in hydrogen feeds and subsequent hydrogen light-off. For H2 streams containing 1,000 p.p.m. CO, H2 light-off is complete by 30 (composite function)C, which is significantly better than for traditional PtRu nano-alloys (85 (composite function)C), monometallic mixtures of nanoparticles (93 (composite function)C) and pure Pt particles (170 ( composite function)C). Density functional theory studies suggest that the enhanced catalytic activity for the core-shell nanoparticle originates from a combination of an increased availability of CO-free Pt surface sites on the Ru@Pt nanoparticles and a hydrogen-mediated low-temperature CO oxidation process that is clearly distinct from the traditional bifunctional CO oxidation mechanism.