George Holding began his career in law before transitioning to public service, serving as legislative counsel to U.S. Senator Jesse Helms. He later worked for a prominent Raleigh law firm and the U.S. Attorney's office for the Eastern District of North Carolina. Holding was nominated by President George W. Bush to succeed Frank Whitney as U.S. Attorney for the Eastern District of North Carolina, a role in which he prosecuted high-profile cases, including those against former North Carolina Governor Mike Easley and former U.S. Senator John Edwards on campaign finance charges. He also led the prosecution of a significant terrorism-related case involving the Raleigh jihad group. Holding's professional expertise and leadership capabilities were recognized with an Honorary Officer of the Order of the British Empire (OBE) award for services to UK-US relations.

George Holding's strategic philosophy is rooted in a distinctive blend of legal enforcement and international diplomacy. His prosecutorial efforts against high-profile political figures on campaign finance charges reflect a stringent approach to political integrity. Holding's involvement in terrorism-related cases, particularly the Raleigh jihad group, indicates a robust stance on national security. This juxtaposition of roles—prosecuting political figures while handling national security cases—reveals a calculated approach to balancing political and legal spheres.