This paper describes a simple strategy for the ultratrace level detection of Pb2+ ion based on G-quadruplex DNA and an electrochemically reduced graphene oxide (ERGO) electrode. First, ERGO was formed on a glassy carbon electrode (GCE) by the reduction of graphene oxide (GO) using cyclic voltammetry. Subsequently, a methylene blue (MB)-tagged, guanine-rich DNA aptamer (Apt) was attached to the surface of ERGO via π-π interaction, leading to the Apt-modified ERGO electrode. The presence of Pb2+ could generate the folding of Apt to a G-quadruplex structure. The formation of G-quadruplex resulted in detaching the Apt from the ERGO/GCE, leading to a change in redox current of the MB tag. Electrochemical measurements showed the proposed sensor had an exceptional sensitivity for Pb2+ with a linear range from 10−15 to 10−9 M and a detection limit of 0.51 fM. The sensor also exhibited high selectivity for Pb2+, as well as many other advantages, such as stability, reproducibility, regeneration, as well as simple fabrication and operation processes.