In this article, a simple, highly sensitive and selective electrochemical DNAzyme sensor for Pb2þ was developed on the basis of a 8–17 DNAzyme cleavage-induced template-independent polymerization and alkaline phosphatase amplification strategy. The hairpin-like substrate strand (HP DNA) of 8–17 DNAzyme was firstly immobilized onto the electrode. In the presence of Pb2þ and the catalytic strand of 8–17 DNAzyme, the HP DNA could be cleaved to expose the free 3′-OH terminal, which could be then utilized for the cascade operation by terminal deoxynucleotidyl transferase (TdTase) for the base extension to incorporate biotinylated dUTP (dUTP-biotin). The further conjugated streptavidin-labeled alkaline phosphatase (SA-ALP) then catalyzed conversion of electrochemically inactive 1-naphthyl phosphate (1- NP) for the generation of electrochemical response signal. The currently fabricated Pb2þ sensor effectively combines triply cascade amplification effects including cyclic Pb2þ-dependent DNAzyme cleavage, TdTase-mediated base extension and enzymatic catalysis of ALP. An impressive detection limit of 0.043 nM toward Pb2þ with an excellent selectivity could be ultimately obtained, which was superior than most of the electrochemical methods. Thus, the developed amplification strategy opens a promising avenue for the detection of metal ions and may extend for the detection of other nucleic acid-related analytes