A novel quartz crystal microbalance (QCM) sensor has been developed for highly selective and sensitive detection of Pb2+ by exploiting the catalytic effect of Pb2+ ions on the leaching of gold nanoparticles from the surface of a QCM sensor. The use of self-assembled gold nanoparticles (AuNPs) strongly enlarges the size of the interface and thus amplifies the analytical response resulting from the loss of mass. This results in a very low detection limit for Pb2+ (30 nM). The high selectivity is demonstrated by studying the effect of potentially interfering ions both in the absence and presence of Pb2+ ions. This simple and well reproducible sensor was applied to the determination of lead in the spiked drinking water. This work provides a novel strategy for fabricating QCM sensors towards Pb2+ in real samples.