A cross-domain ESD protection scheme is disclosed. Embodiments include coupling a first power clamp to a first power rail and a first ground rail; providing a first NMOS transistor having a first source, a first drain, and a first gate; coupling the first source to a second ground rail; providing a first PMOS transistor having a second source, a second drain, and a second gate; coupling the second source to the first power rail; and providing, via the first power clamp, a signal to turn on the first NMOS transistor during an ESD event that occurs at the first power rail.