Electrostatic discharge (ESD) is still a challenging reliability issue for integrated circuits (ICs) in advanced CMOS technology. With the development of ICs toward system-on-chip (SoC) applications, it has been common to integrate multiple separated power domains into a single chip for power management or noise isolation considerations. Besides, the fabricated transistors with thinner gate oxide for high-speed operation cause the ICs more sensitive to charged-device model (CDM) ESD events, especially under cross-domain stresses. The traditional cross-domain CDM ESD protection would result in some restrictions on circuit applications or cause some performance degradation. Thus, a new protection design with stacking footer/header metal-oxide-semiconductor (MOS) structure against cross-domain CDM ESD stresses was proposed in this work and verified in 0.18-mu m CMOS technology. The proposed design got higher ESD robustness under CDM and HBM (human body model) ESD tests. Moreover, the CDM robustness of different stacking-MOS protection designs was also investigated in detail.