North Platte sits on Interstate 80, the main east–west highway across the country, roughly halfway between Omaha and the Wyoming border. It is a natural stopping point on a cross-country drive: Omaha is about 360 kilometres to the east, Denver is about 460 kilometres to the southwest via I-76.
The North Platte Regional Airport (LBF) has small regional flights, but most visitors arrive by car. Greyhound stops here on its transcontinental routes. Amtrak does not serve North Platte on a regular scheduled basis, though Union Pacific's Bailey Yard is right here — a reminder that the railroad built this city even if it no longer carries passengers through it.