Dynamic control of nanomaterial assembly states in response to chemical stimuli is critical in making multi-component materials with interesting properties. Previous work has shown that a Pb²⁺-specific DNAzyme allowed dynamic control of gold nanoparticle aggregation states in response to Pb²⁺, and the resulting color change from blue aggregates to red dispersed particles can be used as a convenient way of sensing Pb²⁺. However, a small piece of DNA (called invasive DNA) and low ionic strength (∼30 mM) were required for the process, limiting the scope of application in assembly and sensing. To overcome this limitation, a series of asymmetric DNAzymes, in which one of the two substrate binding regions is longer than the other, has been developed. With such a system, we demonstrated Pb²⁺-induced disassembly of gold nanoparticle aggregates and corresponding color change at room temperature without the need for invasive DNA, while also making the system more tolerant to ionic strength (33–100 mM). The optimal lengths of the long and short arms were determined to be 14 and 5 base pairs, respectively. In nanoparticle aggregates, the activity of the DNAzyme increased with decreasing ionic strength of the reaction buffer. This simpler and more versatile system allows even better dynamic control of nanoparticle aggregation states in response to chemical stimuli such as Pb²⁺, and can be used in a wider range of applications for colorimetric sensing of metal ions.