A state’s competitiveness in the innovation economy stems from the extent of its involvement in the global economy, its capacity for innovation, and its cultivation of a knowledge-based workforce. Massachusetts, California, Ontario, Maryland, and Washington rank highest among North American states in ITIF’s index scoring subnational innovation competitiveness. Canadian provinces overrepresent among North America’s most competitive states in the innovation economy. Ontario ranks third, British Columbia fourth, and Quebec nineth. Mexico’s industrially intensive states are among its most innovative: Nuevo Leon, Baja California, Chihuahua, and Tamaulipas are some of the highest-ranking Mexican states. Cross-border innovation clusters are taking shape in the Pacific Northwest’s life-sciences industry and in the next-generation automobile and semiconductor industries near the U.S.-Mexico border. Canadian, U.S., and Mexican states should leverage each other’s comparative advantages in different phases of innovation in order to build North American global value chains that are cost-competitive with Asia.