In this study, Cu and Zn isotopic measurements were optimized using a large-geometry high-resolution multiple collector inductively coupled plasma mass spectrometer. A single-column anion-exchange separation of Cu and Zn from igneous rocks was performed using a strong anion resin AG-MP-1M. The Cu and Zn isotopic compositions were calibrated by a sample standard bracketing method, while a Cu internal element spike was also used to correct for mass bias in the Zn measurements. A series of experiments were developed to evaluate the influence of various parameters on the isotopic measurements of Cu and Zn. Acid molarity, matrix (Na, Ti, Mg, and Ni), and residual HF and HCl could significantly affect the accuracy and precision of the results. The long-term external precision was better than ± 0.04‰ (2SD) for both the δ65Cu and δ66Zn. The Cu and Zn isotopic compositions of all igneous rock standards measured in this study agree well with previously published data within uncertainties.