A DNA library with glycyl–histidine-functionalized tertiary amine moiety modification at the cleavage junction was used for in vitro selection of Zn2+-dependent DNAzyme. Four DNAzymes were isolated and each of these DNAzymes displays different cooperative binding of metal ions. An interesting relationship between the number of metal ions involved in DNAzyme catalysis and selectivity was established, and this study showed that it could be a useful way to develop highly specific metal sensors.